Os autores gostariam de agradecer ao Dr. Jumpei Morimoto e Dr. Todd Doran para a assistência valiosa. Este trabalho foi apoiado por um contrato do NHLBI (no1-HV-00242).

<ol>
	<li>Xiao, X., Yu, P., Lim, H. -. S., Sikder, D., Kodadek, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+and+Synthesis+of+a+Cell-Permeable+Synthetic+Transcription+Factor+Mimic.">Design and Synthesis of a Cell-Permeable Synthetic Transcription Factor Mimic.</a> Journal of Combinatorial Chemistry. 9, 592-600 (2007).</li><li>Miller, S. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Proteolytic+Studies+of+Homologous+Peptide+and+N-Substituted+Glycine+Peptoid+Oligomers.">Proteolytic Studies of Homologous Peptide and N-Substituted Glycine Peptoid Oligomers.</a> Bioorganic &amp; Medicinal Chemistry Letters. 4, 2657-2662 (1994).</li><li>Grauer, A., Konig, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peptidomimetics+-+A+Versatile+Route+to+Biologically+Active+Compounds.">Peptidomimetics - A Versatile Route to Biologically Active Compounds.</a> European Journal of Organic Chemistry. 30, 5099-5111 (2009).</li><li>Zuckermann, R. N., Kerr, J. M., Kent, S. B. H., Moos, W. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficient+method+for+the+preparation+of+peptoids+[oligo(N-substituted+glycines)]+by+submonomer+solid-phase+synthesis.">Efficient method for the preparation of peptoids [oligo(N-substituted glycines)] by submonomer solid-phase synthesis.</a> Journal of the American Chemical Society. 114, 10646-10647 (1992).</li><li>Figliozzi, G. M., Goldsmith, R., Ng, S. C., Banville, S. C., Zuckermann, R. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+N-substituted+glycine+peptoid+libraries.">Synthesis of N-substituted glycine peptoid libraries.</a> Methods in Enzymology. 267, 437-447 (1996).</li><li>Seebach, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=beta-peptides:+Synthesis+by+Arndt-Eistert+homologation+with+concomitant+peptide+coupling.+Structure+determination+by+NMR+and+CD+spectroscopy+and+by+X-ray+crystallography.+Helical+secondary+structure+of+a+beta-hexapeptide+in+solution+and+its+stability+towards+pepsin.">beta-peptides: Synthesis by Arndt-Eistert homologation with concomitant peptide coupling. Structure determination by NMR and CD spectroscopy and by X-ray crystallography. Helical secondary structure of a beta-hexapeptide in solution and its stability towards pepsin.</a> Helv Chim Acta. 79, 913-941 (1996).</li><li>Lam, K. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+New+Type+of+Synthetic+Peptide+Library+for+Identifying+Ligand-Binding+Activity.">A New Type of Synthetic Peptide Library for Identifying Ligand-Binding Activity.</a> Nature. 354, 82-84 (1991).</li><li>Simon, R. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peptoids+-+a+Modular+Approach+to+Drug+Discovery.">Peptoids - a Modular Approach to Drug Discovery.</a> Proceedings of the National Academy of Sciences of the United States of America. 89, 9367-9371 (1992).</li><li>Burkoth, T. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toward+the+synthesis+of+artificial+proteins:+the+discovery+of+an+amphiphilic+helical+peptoid+assembly.">Toward the synthesis of artificial proteins: the discovery of an amphiphilic helical peptoid assembly.</a> Chem Biol. 9, 647-654 (2002).</li><li>Alluri, P. G., Reddy, M. M., Bachhawat-Sikder, K., Olivos, H. J., Kodadek, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Isolation+of+protein+ligands+from+large+peptoid+libraries.">Isolation of protein ligands from large peptoid libraries.</a> Journal of the American Chemical Society. 125, 13995-14004 (2003).</li><li>Lim, H. S., Archer, C. T., Kodadek, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+a+peptoid+inhibitor+of+the+proteasome+19S+regulatory+particle.">Identification of a peptoid inhibitor of the proteasome 19S regulatory particle.</a> Journal of the American Chemical Society. 129, 7750-7751 (2007).</li><li>Wrenn, S. J., Weisinger, R. M., Halpin, D. R., Harbury, P. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthetic+ligands+discovered+by+in+vitro+selection.">Synthetic ligands discovered by in vitro selection.</a> Journal of the American Chemical Society. 129, 13137-13143 (2007).</li><li>Aina, O. H., Marik, J., Liu, R. W., Lau, D. H., Lam, K. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+novel+targeting+peptides+for+human+ovarian+cancer+cells+using+&amp;#34;one-bead+one-compound&amp;#34;+combinatorial+libraries.">Identification of novel targeting peptides for human ovarian cancer cells using &amp;#34;one-bead one-compound&amp;#34; combinatorial libraries.</a> Mol Cancer Ther. 4, 806-813 (2005).</li><li>Udugamasooriya, D. G., Dineen, S. P., Brekken, R. A., Kodadek, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Peptoid+&#8220;Antibody+Surrogate&#8221;+That+Antagonizes+VEGF+Receptor+2+Activity.">A Peptoid &#8220;Antibody Surrogate&#8221; That Antagonizes VEGF Receptor 2 Activity.</a> Journal of the American Chemical Society. 130, 5744-5752 (2008).</li><li>Shah, N. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oligo(+N-aryl+glycines):+A+New+Twist+on+Structured+Peptoids.">Oligo( N-aryl glycines): A New Twist on Structured Peptoids.</a> Journal of the American Chemical Society. 130, 16622-16632 (2008).</li><li>Chongsiriwatana, N. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peptoids+that+mimic+the+structure,+function,+and+mechanism+of+helical+antimicrobial+peptides.">Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides.</a> Proceedings of the National Academy of Sciences of the United States of America. 105, 2794-2799 (2008).</li><li>Paul, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=N-Naphthyl+Peptoid+Foldamers+Exhibiting+Atropisomerism.">N-Naphthyl Peptoid Foldamers Exhibiting Atropisomerism.</a> Organic Letters. 14, 926-929 (2012).</li><li>Crapster, J. A., Guzei, I. A., Blackwell, H. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+peptoid+ribbon+secondary+structure.">A peptoid ribbon secondary structure.</a> Angewandte Chemie. 52, 5079-5084 (2013).</li><li>Gorske, B. C., Stringer, J. R., Bastian, B. L., Fowler, S. A., Blackwell, H. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+strategies+for+the+design+of+folded+peptoids+revealed+by+a+survey+of+noncovalent+interactions+in+model+systems.">New strategies for the design of folded peptoids revealed by a survey of noncovalent interactions in model systems.</a> J Am Chem Soc. 131, 16555-16567 (2009).</li><li>Stringer, J. R., Crapster, J. A., Guzei, I. A., Blackwell, H. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Extraordinarily+robust+polyproline+type+I+peptoid+helices+generated+via+the+incorporation+of+alpha-chiral+aromatic+N-1-naphthylethyl+side+chains.">Extraordinarily robust polyproline type I peptoid helices generated via the incorporation of alpha-chiral aromatic N-1-naphthylethyl side chains.</a> J Am Chem Soc. 133, 15559-15567 (2011).</li><li>Huang, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+threaded+loop+conformation+adopted+by+a+family+of+peptoid+nonamers.">A threaded loop conformation adopted by a family of peptoid nonamers.</a> Journal of the American Chemical Society. 128, 1733-1738 (2006).</li><li>Lee, J. H., Kim, H. S., Lim, H. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+and+Facile+Solid-Phase+Synthesis+of+Conformationally+Constrained+Bicyclic+Peptoids.">Design and Facile Solid-Phase Synthesis of Conformationally Constrained Bicyclic Peptoids.</a> Organic Letters. 13, 5012-5015 (2011).</li><li>Gao, Y., Kodadek, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+and+Screening+of+Stereochemically+Diverse+Combinatorial+Libraries+of+Peptide+Tertiary+Amides.">Synthesis and Screening of Stereochemically Diverse Combinatorial Libraries of Peptide Tertiary Amides.</a> Chem Biol. 20, 360-369 (2013).</li><li>Urban, J., Vaisar, T., Shen, R., Lee, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lability+of+N-alkylated+peptides+towards+TFA+cleavage.">Lability of N-alkylated peptides towards TFA cleavage.</a> Int J Pept Protein Res. 47, 182-189 (1996).</li><li>Rzuczek, S. G., Gao, Y., Tang, Z., Thornton, C. A., Kodadek, T., Disney, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Features+of+Modularly+Assembled+Compounds+That+Impart+Bioactivity+Against+an+RNA+Target.">Features of Modularly Assembled Compounds That Impart Bioactivity Against an RNA Target.</a> ACS Chemical Biology. 8 (10), 2312-2321 (2013).</li><li>Thern, B., Rudolph, J., Jung, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Triphosgene+as+highly+efficient+reagent+for+the+solid-phase+coupling+of+N-alkylated+amino+acids&#8212;total+synthesis+of+cyclosporin+O.">Triphosgene as highly efficient reagent for the solid-phase coupling of N-alkylated amino acids&#8212;total synthesis of cyclosporin O.</a> Tetrahedron Letters. 43, 5013-5016 (2002).</li><li>Sleebs, M. M., Scanlon, D., Karas, J., Maharani, R., Hughes, A. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Total+Synthesis+of+the+Antifungal+Depsipeptide+Petriellin+A.">Total Synthesis of the Antifungal Depsipeptide Petriellin A.</a> J Org Chem. 76, 6686-6693 (2011).</li><li>Vaisar, T., Urban, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gas-phase+fragmentation+of+protonated+mono-N-methylated+peptides.+Analogy+with+solution-phase+acid-catalyzed+hydrolysis.">Gas-phase fragmentation of protonated mono-N-methylated peptides. Analogy with solution-phase acid-catalyzed hydrolysis.</a> Journal of Mass Spectrometry. 33, 505-524 (1998).</li><li>Creighton, C. J., Romoff, T. T., Bu, J. H., Goodman, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanistic+studies+of+an+unusual+amide+bond+scission.">Mechanistic studies of an unusual amide bond scission.</a> Journal of the American Chemical Society. 121, 6786-6791 (1999).</li><li>Sewald, N., Sewald, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficient,+racemization-free+peptide+coupling+of+N-alkyl+amino+acids+by+using+amino+acid+chlorides+generated+in+situ--total+syntheses+of+the+cyclopeptides+cyclosporin+O+and+omphalotin+A.">Efficient, racemization-free peptide coupling of N-alkyl amino acids by using amino acid chlorides generated in situ--total syntheses of the cyclopeptides cyclosporin O and omphalotin A.</a> Angewandte Chemie (International ed. in English). 41, 4661-4663 (2002).</li><li>Astle, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Seamless+Bead+to+Microarray+Screening:+Rapid+Identification+of+the+Highest+Affinity+Protein+Ligands+from+Large+Combinatorial+Libraries.">Seamless Bead to Microarray Screening: Rapid Identification of the Highest Affinity Protein Ligands from Large Combinatorial Libraries.</a> Chem Biol. 17, 38-45 (2010).</li><li>Strohalm, M., Kavan, D., Novak, P., Volny, M., Havlicek, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=mMass+3:+a+cross-platform+software+environment+for+precise+analysis+of+mass+spectrometric+data.">mMass 3: a cross-platform software environment for precise analysis of mass spectrometric data.</a> Anal Chem. 82, 4648-4651 (2010).</li></ol>

Os autores declaram que não têm interesses financeiros concorrentes.

Peptídeo amidas terciárias (PTAs) são uma superfamília de oligômeros peptidomiméticas. Além dos peptídeos bem estudadas, peptoids e peptídeos N-metilados, uma grande parte dos compostos que compõem a família permanece pouco estudado, majoritariamente devido à falta de método sintético para acessar gerais peptídeos N-alquilados. Aqui, descrevemos um método eficiente para sintetizar APCs com os blocos de construção quirais derivados de amino ácidos. Anteriormente, relataram usar uma nova rota sub-monôm...

Os peptidomiméticos são compostos que imitam a estrutura dos péptidos naturais. Eles são concebidos para reter a bioactividade ao superar alguns dos problemas associados com os péptidos naturais, incluindo a permeabilidade celular e a estabilidade contra a proteólise 1-3. Devido à natureza oligomérica destes compostos, grandes bibliotecas sintéticas pode ser facilmente acedido através de vias sintéticas monoméricas ou sub-monoméricos 4-7. Uma das classes mais estudados da peptidomimetics é peptoids. Peptóides são oligómeros de glicinas N-alquilados que podem ser facilmente sintetizados utilizando uma estratégia de sub-monómero de 8, 9. Muitos ligantes de proteínas úteis foram identificados com sucesso desde a triagem de grandes bibliotecas peptoid sintética contra alvos da proteína 1, 10-14. No entanto, os &quot;hits&quot; identificados a partir de bibliotecas peptoid raramente arquivar muito elevada afinidade para proteínas alvo 1,10-14,22. Uma major diferença entre peptóides e péptidos naturais é que a maioria dos peptóides geralmente não têm a capacidade de formar estruturas secundárias devido à falta de centros quirais e restrições conformacionais. Para resolver este problema, várias estratégias foram desenvolvidas ao longo da última década, em grande parte, com foco na modificação de cadeias laterais contidos os principais átomos de nitrogênio da cadeia de 15-22. Recentemente, desenvolvemos uma nova via de síntese para introduzir as cadeias laterais de aminoácidos naturais em uma espinha dorsal peptoid para criar péptidos amidas terciárias 23. Peptídeo amidas terciárias (PTA) são uma super-família de peptidomiméticos que incluem mas não estão limitados a péptidos (R 2 = H), peptóides (R1 = H) e os péptidos N-metilados (R1 ≠ H, R2 = Me) . (Ver Figura 1) A via sintética emprega aminoácidos de ocorrência natural como fonte de quiralidade e cadeias laterais na45; de carbono, e as aminas primárias disponíveis comercialmente para proporcionar N-substituições. Por conseguinte, um espaço maior do que o químico de péptidos simples, peptóides ou péptidos N-metilados podem ser exploradas. Os espectros de dicroísmo circular demonstraram que as moléculas de PTA são altamente estruturado em solução. Caracterização de um dos complexos de proteína-PTA mostra claramente que os constrangimentos conformacionais de ATP são necessários para a ligação. Recentemente, nós também descobrimos que algumas das moléculas de PTA possuem melhorada a permeabilidade celular do que os seus homólogos peptoid e peptídicas. Acreditamos que essas bibliotecas PTA pode ser uma boa fonte de ligantes de alta afinidade para proteínas alvo. Neste artigo, vamos discutir a síntese de uma amostra de um talão de um composto (OBOC) biblioteca de PTA em detalhes, juntamente com alguns melhores condições para o acoplamento e clivagem destes compostos.

<table border="0" cellpadding="0" cellspacing="0" width="889">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">2,4,6 trimethylpyridine</td>
			<td style="width:169px;">ACROS</td>
			<td style="width:160px;">161950010</td>
			<td style="width:311px;">CAS:108-75-8</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">2-morpholinoethanamine</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">06680&#160;</td>
			<td>CAS:2038-03-1&#160;&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">48% HBr Water solution</td>
			<td style="width:169px;">ALFA AESAR</td>
			<td style="width:160px;">AA14036AT</td>
			<td>CAS:10035-10-6</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Acetaldehyde</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">402788</td>
			<td>CAS:75-07-0&#160;&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Acetonitrile</td>
			<td style="width:169px;">Fisher</td>
			<td style="width:160px;">SR015AA-19PS</td>
			<td>CAS:75-05-8</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Anhydrous Tetrahydrofuran (THF)</td>
			<td style="width:169px;">EMD</td>
			<td style="width:160px;">EM-TX0277-6&#160;</td>
			<td>CAS:109-99-9</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Benzylamine</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">185701</td>
			<td>CAS:100-46-9</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">bis(trichloromethyl) carbonate (BTC)</td>
			<td style="width:169px;">ACROS</td>
			<td style="width:160px;">258950050</td>
			<td>CAS:32315-10-9</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Bromoacetic acid</td>
			<td style="width:169px;">ACROS</td>
			<td style="width:160px;">106570010</td>
			<td>CAS:79-08-3</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Chloranil</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">23290</td>
			<td>CAS:118-75-2</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Cyclohexanemethylamine</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">101842</td>
			<td>CAS:3218-02-8</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;">D2O</td>
			<td style="width:169px;">Cambridge Isotope</td>
			<td style="width:160px;">DLM-4-99.8-1000</td>
			<td>CAS:7789-20-0</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">D-alanine</td>
			<td style="width:169px;">Anaspec</td>
			<td style="width:160px;">61387-100</td>
			<td>CAS:338-69-2&#160;&#160;</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">Dichloromethane (DCM)</td>
			<td style="width:169px;">Fisher</td>
			<td style="width:160px;">BJ-NS300-20</td>
			<td>CAS:75-09-2</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">Dimethylformamide (DMF)</td>
			<td style="width:169px;">Fisher</td>
			<td style="width:160px;">BJ-076-4</td>
			<td>CAS:68-12-2</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">Ethylene glycol</td>
			<td style="width:169px;">Oakwood</td>
			<td style="width:160px;">44710</td>
			<td>CAS:107-21-1</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">Isopentylamine</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">W321907</td>
			<td>CAS:107-85-7</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">KBr</td>
			<td style="width:169px;">ACROS</td>
			<td style="width:160px;">424070025</td>
			<td>CAS:7758-02-3</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">L-alanine</td>
			<td style="width:169px;">Anaspec</td>
			<td style="width:160px;">61385-100</td>
			<td>CAS:56-41-7&#160;</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">3-Methoxypropylamine</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">M25007</td>
			<td>CAS:5332-73-0</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">2-Methoxyethylamine</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">143693</td>
			<td>CAS:109-85-3</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">N-(3-Aminopropyl)-2-pyrrolidinone</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">136565&#160;</td>
			<td>CAS:7663-77-6&#160;</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">N,N&#39;-Diisopropylcarbodiimide (DIC)</td>
			<td style="width:169px;">ACROS</td>
			<td style="width:160px;">115211000</td>
			<td>CAS:693-13-0</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">N,N-Diisopropylethylamine (DIPEA)</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">D125806</td>
			<td>CAS:7087-68-5</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;">NaNO2</td>
			<td style="width:169px;">ACROS</td>
			<td style="width:160px;">424340010</td>
			<td>CAS:7631-99-4</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:21px;width:249px;">NAOD 40% solution in water</td>
			<td style="width:169px;">ACROS</td>
			<td style="width:160px;">200058-506</td>
			<td>CAS:7732-18-5</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Piperidine</td>
			<td style="width:169px;">ALFA AESAR</td>
			<td style="width:160px;">A12442-AE</td>
			<td>CAS:110-89-4</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Piperonylamine</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">P49503&#160;</td>
			<td>CAS:2620-50-0</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Propylamine</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">240958</td>
			<td>CAS:107-10-8</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Trifluoroacetic acid</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">299537</td>
			<td>CAS:76-05-1</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">&#945;-Cyano-4-hydroxycinnamic acid&#160;</td>
			<td style="width:169px;">Sigma-Aldrich</td>
			<td style="width:160px;">39468</td>
			<td>CAS:28166-41-8&#160;&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">&#945;-ketoglutarate</td>
			<td style="width:169px;">ALFA AESAR</td>
			<td style="width:160px;">AAA10256-22</td>
			<td style="width:311px;">CAS:328-50-7</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Tentagel Resin with RINK linker</td>
			<td style="width:169px;">Rapp-Polymere</td>
			<td style="width:160px;">S30023</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Alanine transaminase</td>
			<td style="width:169px;">Roche</td>
			<td style="width:160px;">10105589001</td>
			<td>AKA: Glutamate-Pyruvate Transaminase (GPT)</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:249px;">Incubator</td>
			<td style="width:169px;">New Brunswick Scientific</td>
			<td style="width:160px;">Innova44</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">NMR</td>
			<td style="width:169px;">Bruker</td>
			<td style="width:160px;">400MHz</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">MALDI mass spectrometer</td>
			<td style="width:169px;">Applied Biosystems&#160;</td>
			<td style="width:160px;">4800 MALDI-TOF/TOF</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Lyophilizer</td>
			<td style="width:169px;">SP Scientific</td>
			<td style="width:160px;">VirTis benchtop K</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Syringe reactor</td>
			<td style="width:169px;">INTAVIS&#160;</td>
			<td style="width:160px;">Reaction Column</td>
			<td>3ml, 5ml, 10ml, 20ml</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Vacuum manifold&#160;</td>
			<td style="width:169px;">Promega</td>
			<td style="width:160px;">A7231</td>
			<td>Vac-Man</td>
		</tr>
	</tbody>
</table>

split-and-pool synthesis and characterization of peptide tertiary amide library

Peptidomimetics são excelentes fontes de proteínas ligantes. A natureza oligomérica destes compostos nos permite aceder a grandes bibliotecas sintéticos em fase sólida, utilizando química combinatória. Uma das classes mais bem estudados da peptidomimetics é peptoids. Peptóides são fáceis de sintetizar e têm mostrado ser resistentes à proteólise e célula-permeável. Ao longo da última década, muitos ligantes protéicos úteis foram identificados através de pesquisa de bibliotecas peptoid. No entanto, a maioria dos ligantes identificados a partir de bibliotecas peptoid não exibem uma elevada afinidade, com raras excepções. Isto pode ser devido, em parte, à falta de centros quirais e restrições conformacionais em moléculas peptoid. Recentemente, descrevemos uma nova rota sintética para acessar peptídeo amidas terciárias (PTAs). APCs são uma super família de peptidomiméticos que incluem mas não estão limitados a peptídeos, peptóides e peptídeos N-metilados. Com cadeias laterais em ambos α-carbono e principais átomos de nitrogênio da cadeia,a conformação, estas moléculas são grandemente limitado por impedimento estérico e alílico 1,3 estirpe. (Figura 1) O nosso estudo sugere que estas moléculas PTA são altamente estruturado em solução e pode ser utilizada para identificar ligandos de proteína. Acreditamos que estas moléculas podem ser uma fonte de futuro ligandos proteicos de alta afinidade. Aqui nós descrevemos o método sintético que combina o poder de ambos split-and-piscina e estratégias sub-monômero para sintetizar uma amostra de um talão de um composto (OBOC) biblioteca de PTAs.

Aqui nós mostramos três espectros MALDI representativas de um trímero PTA com vinculador. Como mostrado na Figura 6A, quando clivada sob condições de temperatura ambiente, utilizando 50% de solução de TFA / DCM, degradação significativa é observada. Na Figura 6A, o pico 593 e 484 correspondem ao ligante e o trímero de PTA, respectivamente, mostram que a molécula inteira foi sintetizado com sucesso no talão mas degradados durante a clivagem. Quando clivada sob a condição d...

Watch this Scientific Journal Video about Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library at JoVE.com

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library

Peptídeo amidas terciárias (PTA) são uma super família de peptidomiméticos que incluem mas não estão limitados a péptidos, peptóides e peptídeos N-metilados. Aqui nós descrevemos um método sintético que combina split-and-piscina e estratégias sub-monômero para sintetizar um talão biblioteca de um composto de PTAs.

Split-and-piscina Síntese e Caracterização de Peptídeos Terciário Amide Biblioteca

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid ...

split-pool-synthesis-characterization-peptide-tertiary-amide

Research

Education

JoVE Core

JoVE Journal

Organic Chemistry

Chemistry

Unit 1

Carboxylic Acid Derivatives

SCIENTISTS IN ACTION

18.0K visualizações.  The Scripps Research Institute.  Peptídeo amidas terciárias (PTA) são uma super família de peptidomiméticos que incluem mas não estão limitados a péptidos, peptóides e peptídeos N-metilados. Aqui nós descrevemos um método sintético que combina split-and-piscina e estratégias sub-monômero para sintetizar um talão biblioteca de um composto de PTAs. 

Vídeo: Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization

The traditional strategy for the introduction of chemical functionalities is the use of solid-phase synthesis by appending suitably modified phosphoramidite precursors to the nascent chain. However, the conditions used during the synthesis and the restriction to rather short sequences hamper the applicability of this methodology. On the other hand, modified nucleoside triphosphates are activated building blocks that have been employed for the mild introduction of numerous functional groups into nucleic acids, a strategy that paves the way for the use of modified nucleic acids in a wide-ranging palette of practical applications such as functional tagging and generation of ribozymes and DNAzymes. One of the major challenges resides in the intricacy of the methodology leading to the isolation and characterization of these nucleoside analogues.
	
	In this video article, we present a detailed protocol for the synthesis of these modified analogues using phosphorous(III)-based reagents. In addition, the procedure for their biochemical characterization is divulged, with a special emphasis on primer extension reactions and TdT tailing polymerization. This detailed protocol will be of use for the crafting of modified dNTPs and their further use in chemical biology.

The protocol described herein aims to explain and abridge the numerous obstacles in the way of the intricate route leading to modified nucleoside triphosphates. Consequently, this protocol facilitates both the synthesis of these activated building-blocks and their availability for practical applications.

Nucleosídeos Trisfosfatos - Da síntese à Caracterização Bioquímica

The  traditional strategy for the introduction of chemical functionalities is the  use of solid-phase synthesis by appending suitably modified ...

Química

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. Isonicotinic acid, or its derivatives, are coupled to variable length diaminoalkane chains under an inert atmosphere in anhydrous DMF or DMSO with the use of a weak base, triethylamine, and a coupling agent, 1-propylphosphonic anhydride. The products precipitate from solution upon formation or can be precipitated by the addition of water. If desired, the ligands can be further purified by recrystallization from hot water. Dinuclear platinum complex synthesis using the bispyridine ligands is done in hot water using transplatin. The most informative of the chemical characterization techniques to determine the structure and gross purity of both the bispyridine ligands and the final platinum complexes is 1H NMR with particular analysis of the aromatic region of the spectra (7-9 ppm). The platinum complexes have potential application as anticancer agents and the synthesis method can be modified to produce trinuclear and other multinuclear complexes with different hydrogen bonding functionality in the bridging ligand.

This protocol describes the use of amide coupling reactions of isonicotinic acid and diaminoalkanes to form bridging ligands suitable for use in the synthesis of multinuclear platinum complexes, which combine aspects of the anticancer drugs BBR3464 and picoplatin.

Acoplamento de amida de reacção para a síntese de ligandos baseados em Bispyridine e sua complexação com platina como agentes anticancerígenos dinucleares

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. ...

Synthesis and Characterization of Functionalized Metal-organic Frameworks

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and technological applications. Their signature property is their ultrahigh porosity, which however imparts a series of challenges when it comes to both constructing them and working with them. Securing desired MOF chemical and physical functionality by linker/node assembly into a highly porous framework of choice can pose difficulties, as less porous and more thermodynamically stable congeners (e.g., other crystalline polymorphs, catenated analogues) are often preferentially obtained by conventional synthesis methods. Once the desired product is obtained, its characterization often requires specialized techniques that address complications potentially arising from, for example, guest-molecule loss or preferential orientation of microcrystallites. Finally, accessing the large voids inside the MOFs for use in applications that involve gases can be problematic, as frameworks may be subject to collapse during removal of solvent molecules (remnants of solvothermal synthesis). In this paper, we describe synthesis and characterization methods routinely utilized in our lab either to solve or circumvent these issues. The methods include solvent-assisted linker exchange, powder X-ray diffraction in capillaries, and materials activation (cavity evacuation) by supercritical CO2 drying. Finally, we provide a protocol for determining a suitable pressure region for applying the Brunauer-Emmett-Teller analysis to nitrogen isotherms, so as to estimate surface area of MOFs with good accuracy.

Synthesis, activation, and characterization of intentionally designed metal-organic framework materials is challenging, especially when building blocks are incompatible or unwanted polymorphs are thermodynamically favored over desired forms. We describe how applications of solvent-assisted linker exchange, powder X-ray diffraction in capillaries and activation via supercritical CO2 drying, can address some of these challenges.

Síntese e caracterização de funcionalizados metal-organic frameworks

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and ...

The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes

Herein we report the synthesis of a tridentate phosphine ligand N(CH2PPh2)3 (N-triphosPh) (1) via a phosphorus based Mannich reaction of the hydroxylmethylene phosphine precursor with ammonia in methanol under a nitrogen atmosphere. The N-triphosPh ligand precipitates from the solution after approximately 1 hr of reflux and can be isolated analytically pure via simple cannula filtration procedure under nitrogen. Reaction of the N-triphosPh ligand with [Ru3(CO)12] under reflux affords a deep red solution that show evolution of CO gas on ligand complexation. Orange crystals of the complex [Ru(CO)2{N(CH2PPh2)3}-&#954;3P] (2) were isolated on cooling to RT. The 31P{1H} NMR spectrum showed a characteristic single peak at lower frequency compared to the free ligand. Reaction of a toluene solution of complex 2 with oxygen resulted in the instantaneous precipitation of the carbonate complex [Ru(CO3)(CO){N(CH2PPh2)3}-&#954;3P] (3) as an air stable orange solid. Subsequent hydrogenation of 3 under 15 bar of hydrogen in a high-pressure reactor gave the dihydride complex [RuH2(CO){N(CH2PPh2)3}-&#954;3P] (4), which was fully characterized by X-ray crystallography and NMR spectroscopy. Complexes 3 and 4 are potentially useful catalyst precursors for a range of hydrogenation reactions, including biomass-derived products such as levulinic acid (LA). Complex 4 was found to cleanly react with LA in the presence of the proton source additive NH4PF6 to give [Ru(CO){N(CH2PPh2)3}-&#954;3P{CH3CO(CH2)2CO2H}-&#954;2O](PF6) (6).

The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes

Ruthenium phosphine complexes are widely used for homogeneous catalytic reactions such as hydrogenations. The synthesis of a series of novel tridentate ruthenium complexes bearing the N-triphos ligand N(CH2PPh2)3 is reported. Additionally, the stoichiometric reaction of a dihydride Ru&#8211;N-triphos complex with levulinic acid is described.

A Síntese, Caracterização e Reatividade de uma série de Rutênio<em&gt; N</em&gt; -triphos<sup&gt; Ph</sup&gt; Complexos

Herein we report the synthesis of a tridentate phosphine ligand N(CH2PPh2)3 (N-triphosPh) (1) via a phosphorus based Mannich reaction of the ...

Synthesis, Characterization, and Functionalization of Hybrid Au/CdS and Au/ZnS Core/Shell Nanoparticles

Plasmonic nanoparticles are an attractive material for light harvesting applications due to their easily modified surface, high surface area and large extinction coefficients which can be tuned across the visible spectrum. Research into the plasmonic enhancement of optical transitions has become popular, due to the possibility of altering and in some cases improving photo-absorption or emission properties of nearby chromophores such as molecular dyes or quantum dots. The electric field of the plasmon can couple with the excitation dipole of a chromophore, perturbing the electronic states involved in the transition and leading to increased absorption and emission rates. These enhancements can also be negated at close distances by energy transfer mechanism, making the spatial arrangement of the two species critical. Ultimately, enhancement of light harvesting efficiency in plasmonic solar cells could lead to thinner and, therefore, lower cost devices. The development of hybrid core/shell particles could offer a solution to this issue. The addition of a dielectric spacer between a gold nanoparticles and a chromophore is the proposed method to control the exciton plasmon coupling strength and thereby balance losses with the plasmonic gains. A detailed procedure for the coating of gold nanoparticles with CdS and ZnS semiconductor shells is presented. The nanoparticles show high uniformity with size control in both the core gold particles and shell species allowing for a more accurate investigation into the plasmonic enhancement of external chromophores.

The synthesis of uniform gold nanoparticles coated with semiconductor shells of CdS or ZnS is performed. The semiconductor coating is conducted by first depositing a silver sulfide shell and exchanging the silver cations for zinc or cadmium cations.

Síntese, caracterização e funcionalização de híbrida UA / CDS e Au / ZnS Núcleo / Shell Nanopartículas

Plasmonic nanoparticles are an attractive material for light harvesting applications due to their easily modified surface, high surface area and large ...

Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation

Protein-protein interactions (PPIs) are intimately involved in almost all biological processes and are linked to many human diseases. Therefore, there is a major effort to target PPIs in basic research and in the pharmaceutical industry. Protein-protein interfaces are usually large, flat, and often lack pockets, complicating the discovery of small molecules that target such sites. Alternative targeting approaches using antibodies have limitations due to poor oral bioavailability, low cell-permeability, and production inefficiency.
Using peptides to target PPI interfaces has several advantages. Peptides have higher conformational flexibility, increased selectivity, and are generally inexpensive. However, peptides have their own limitations including poor stability and inefficiency crossing cell membranes. To overcome such limitations, peptide cyclization can be performed. Cyclization has been demonstrated to improve peptide selectivity, metabolic stability, and bioavailability. However, predicting the bioactive conformation of a cyclic peptide is not trivial. To overcome this challenge, one attractive approach it to screen a focused library to screen in which all backbone cyclic peptides have the same primary sequence, but differ in parameters that influence their conformation, such as ring size and position.
We describe a detailed protocol for synthesizing a library of backbone cyclic peptides targeting specific parasite PPIs. Using a rational design approach, we developed peptides derived from the scaffold protein Leishmania receptor for activated C-kinase (LACK). We hypothesized that sequences in LACK that are conserved in parasites, but not in the mammalian host homolog, may represent interaction sites for proteins that are critical for the parasites&#39; viability. The cyclic peptides were synthesized using microwave irradiation to reduce reaction times and increase efficiency. Developing a library of backbone cyclic peptides with different ring sizes facilitates a systematic screen for the most biological active conformation. This method provides a general, fast, and facile way to synthesize cyclic peptides.

A simple and general method for the synthesis of cyclic peptides using microwave irradiation is outlined. This procedure enables the synthesis of backbone cyclic peptides with a collection of different conformations while retaining the side chains and the pharmacophoric moieties., and therefore, allows to screen for the bioactive conformation.

Desenvolvimento de um Backbone cíclica Biblioteca de Peptídeos como potencial antiparasitário Therapeutics Usando Microondas Irradiação

Protein-protein interactions (PPIs) are intimately involved in almost all biological processes and are linked to many human diseases. Therefore, there is ...

Synthesis and Characterization of Supramolecular Colloids

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical properties for applications in photonics, drug delivery and coating technology. Here we present a new family of colloidal building blocks, coined supramolecular colloids, whose self-assembly is controlled through surface-functionalization with a benzene-1,3,5-tricarboxamide (BTA) derived supramolecular moiety. Such BTAs interact via directional, strong, yet reversible hydrogen-bonds with other identical BTAs. Herein, a protocol is presented that describes how to couple these BTAs to colloids and how to quantify the number of coupling sites, which determines the multivalency of the supramolecular colloids. Light scattering measurements show that the refractive index of the colloids is almost matched with that of the solvent, which strongly reduces the van der Waals forces between the colloids. Before photo-activation, the colloids remain well dispersed, as the BTAs are equipped with a photo-labile group that blocks the formation of hydrogen-bonds. Controlled deprotection with UV-light activates the short-range hydrogen-bonds between the BTAs, which triggers the colloidal self-assembly. The evolution from the dispersed state to the clustered state is monitored by confocal microscopy. These results are further quantified by image analysis with simple routines using ImageJ and Matlab. This merger of supramolecular chemistry and colloidal science offers a direct route towards light- and thermo-responsive colloidal assembly encoded in the surface-grafted monolayer.

A protocol for the synthesis and characterization of colloids coated with supramolecular moieties is described. These supramolecular colloids undergo self-assembly upon the activation of the hydrogen-bonds between the surface-anchored molecules by UV-light.

Síntese e Caracterização de Supramoleculares Colloids

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical ...

Synthesis and Characterization of Fe-doped Aluminosilicate Nanotubes with Enhanced Electron Conductive Properties

The goal of the protocol is to synthesize Fe-doped aluminosilicate nanotubes of the imogolite type with the formula (OH)3Al2-xFexO3SiOH. Doping with Fe aims at lowering the band gap of imogolite, an insulator with the chemical formula (OH)3Al2O3SiOH, and at modifying its adsorption properties towards azo-dyes, an important class of organic pollutants of both wastewater and groundwater.
Fe-doped nanotubes are obtained in two ways: by direct synthesis, where FeCl3 is added to an aqueous mixture of the Si and Al precursors, and by post-synthesis loading, where preformed nanotubes are put in contact with a FeCl3&#8226;6H2O aqueous solution. In both synthesis methods, isomorphic substitution of Al3+ by Fe3+ occurs, preserving the nanotube structure. Isomorphic substitution is indeed limited to a mass fraction of ~1.0% Fe, since at a higher Fe content (i.e., a mass fraction of 1.4% Fe), Fe2O3 clusters form, especially when the loading procedure is adopted. The physicochemical properties of the materials are studied by means of X-ray powder diffraction (XRD), N2 sorption isotherms at -196 &#176;C, high resolution transmission electron microscopy (HRTEM), diffuse reflectance (DR) UV-Vis spectroscopy, and &#950;-potential measurements. The most relevant result is the possibility to replace Al3+ ions (located on the outer surface of the nanotubes) by post-synthesis loading on preformed imogolite without perturbing the delicate hydrolysis equilibria occurring during nanotube formation. During the loading procedure, an anionic exchange occurs, where Al3+ ions on the outer surface of the nanotubes are replaced by Fe3+ ions. In Fe-doped aluminosilicate nanotubes, isomorphic substitution of Al3+ by Fe3+ is found to affect the band gap of doped imogolite. Nonetheless, Fe3+ sites on the outer surface of nanotubes are able to coordinate organic moieties, like the azo-dye Acid Orange 7, through a ligand-displacement mechanism occurring in an aqueous solution.

Here, we present a protocol to synthesize and characterize Fe-doped aluminosilicate nanotubes. The materials are obtained by either sol-gel synthesis upon addition of FeCl3&#8226;6H2O to the mixture containing the Si and Al precursors or by post-synthesis ionic exchange of preformed aluminosilicate nanotubes.

Síntese e Caracterização de Fe-dopado alumino nanotubos com propriedades condutoras aprimorados Electron

The goal of the protocol is to synthesize Fe-doped aluminosilicate nanotubes of the imogolite type with the formula (OH)3Al2-xFexO3SiOH. Doping with Fe ...

Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles (PPAs) and Related Biomaterials

Polyamine-based Peptide Amphiphiles (PPAs) are a new class of self-assembling amphiphilic biomaterials-related to the peptide amphiphiles (PAs). Traditional PAs possess charged amino acids as solubilizing groups (lysine, arginine), which are directly connected to a lipid segment or can contain a linker region made of neutral amino acids. Tuning the peptide sequence of PAs can yield diverse morphologies. Similarly, PPAs possess a hydrophobic segment and neutral amino acids, but also contain polyamine molecules as water solubilizing (hydrophilic) groups. As is the case with PAs, PPAs can also self-assemble into diverse morphologies, including small rods, twisted nano-ribbons, and fused nano-sheets, when dissolved in water. However, the presence of both primary and secondary amines on a single polyamine molecule poses a significant challenge when synthesizing PPAs. In this paper, we show a simple protocol, based on literature precedents, to achieve a facile synthesis of PPAs using solid phase peptide synthesis (SPPS). This protocol can be extended to the synthesis of PAs and other similar systems. We also illustrate the steps that are needed for cleavage from the resin, identification, and purification.

Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles PPAs and Related Biomaterials

The synthesis of polyamine-based peptide amphiphiles (PPAs) is a significant challenge due to the presence of multiple amine nitrogens, which requires judicious use of protecting groups to mask these reactive functionalities. In this paper, we describe a facile method for the preparation of these new class of self-assembling molecules.

Facile protocolo para a síntese de auto montagem baseada em poliamina peptídeo Amphiphiles (CAE) e biomateriais relacionados

Polyamine-based Peptide Amphiphiles (PPAs) are a new class of self-assembling amphiphilic biomaterials-related to the peptide amphiphiles (PAs). ...

Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides

This report focuses on the synthesis of an N-terminus 1,2-dithiolane modified self-assembling peptide and the characterization of the resulting self-assembled supramolecular structures. The synthetic route takes advantage of solid-phase peptide synthesis with the on-resin coupling of the dithiolane precursor molecule, 3-(acetylthio)-2-(acetylthiomethyl)propanoic acid, and the microwave-assisted thioacetate deprotection of the peptide N-terminus before final cleavage from the resin to yield the 1,2-dithiolane modified peptide. After the high-performance liquid chromatography (HPLC) purification of the 1,2-dithiolane peptide, derived from the nucleating core of the A&#946; peptide associated with Alzheimer&#39;s disease, the peptide is shown to self-assemble into cross-&#946; amyloid fibers. Protocols to characterize the amyloid fibers by Fourier-transform infrared spectroscopy (FT-IR), circular dichroism spectroscopy (CD) and transmission electron microscopy (TEM) are presented. The methods of N-terminal modification with a 1,2-dithiolane moiety to well-characterized self-assembling peptides can now be explored as model systems to develop post-assembly modification strategies and explore dynamic covalent chemistry on supramolecular peptide nanofiber surfaces.

A protocol for the synthesis of a 1,2-dithiolane modified peptide and the characterization of the supramolecular structures resulting from the peptide self-assembly.