We thank Dr. John Greaves and Ms. Soroosh Sorooshian, Department of Chemistry, University of California, Irvine Mass Spectrometry Facility, for mass spectrometric analyses. We also thank Mr. Jacob Buchanan for helpful discussions, as well as Miss Stephanie J. Conn, Mrs. Shannon M. Huffman (Vreeland), and Miss Alexandra N. Wexler for early stage work on this project. Partial funding was provided by the Central Washington University (CWU) School of Graduate Studies (C.E.M), the CWU Seed Grant Program, and the CWU Faculty Research Program.

<ol>
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The authors have nothing to declare.

Erste Versuche zur Vorbereitung clavatadine A eingetragen eine traditionelle, indirekte Annäherung an Guanidinylierung aus einem geeigneten Aminvorstufe, die in diesem Fall ein Terminal Azid war. Im Mittelpunkt dieser Bemühungen war die Vereinigung der beiden Hälften des Moleküls Carbamate zu konstruieren. Leider sind alle Versuche , ein Azid Reduktion im Vorgriff auf eine geplante Spätstadium Guanidinylierung zu realisieren , waren nicht erfolgreich. 25,26 Diese Rückschläge inspiriert die Ausübung de...

Das Ziel dieses Video ist zu zeigen, wie eine direkte und frühen Guanidinylierung Verfahren unter Verwendung einer terminalen Guanidin-Struktur zu machen ist praktischer, schneller und effizienter als herkömmliche Guanidinylierung Methoden in der organischen Synthese. Die funktionellen Guanidingruppe, auf der Aminosäure Arginin gefunden, ist ein zentrales Strukturelement in vielen komplexen Naturstoffen und Pharmazeutika. Die Entdeckung und Design von neuen Guanidin enthaltenden Naturstoffen und kleinen Molekülen herzustellen, die Notwendigkeit für eine effizientere Guanidinylierung Methode. Die am häufigsten verwendete circuitous Ansatz kennzeichnet die Einführung eines latenten Guanidin-Vorstufe, die in einem späten Stadium in der Synthese entlarvt wird. Im Gegensatz dazu installiert eine einfache Taktik ein geschütztes Guanidin auf einem primären Amin in einem frühen Syntheseroute. Die reaktive Natur von Guanidinen schließt sie im Allgemeinen von den Routineeinsatz ohne eine entsprechende Schutzgruppenstrategie. Traditionell Methodenhinzuzufügen umfasste eine funktionellen Guanidingruppe einen indirekten Ansatz, der am Ende der Synthese durch Zugabe des Guanidins mehrere Schutz Schritten gefolgt beteiligt. Zwei neue Synthesen zeigen die Nachteile der indirekten Guanidinylierung 1,2. Das direkte Verfahren berichtet hierin beinhaltet ein geschütztes Guanidin Reagens mit einem primären Amin früh in der Synthese eines gegebenen Moleküls und Entschützen es dann am Ende der Synthese. Diese Strategie wurde im Einsatz erfolgreich in den letzten Totalsynthese von biologisch aktiven marinen Alkaloide clavatadine A und phidianidine A und B 3,4. Während diese direkte Guanidinylierung Verfahren seine Vorteile hat gegenüber herkömmlichen Methoden der Guanidinylierung hat es noch seine Nachteile. Die chemischen Bedingungen, die die geschützte Guanidin überleben können, werden eingesetzt auf der Schutzgruppe abhängen. Trotz dieser möglichen Nachteile, ist die direkte Guanidinylierung Verfahren ein FreigabestrategieTerminal Guanidine primäre Amine zur Verwendung in der Synthese von komplexen organischen Molekülen Verwendung hinzuzufügen.

<table border="0" cellpadding="0" cellspacing="0" width="835">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Chloroform-d</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">612200-100G</td>
			<td style="width:419px;">99.8% D, 0.05% v/v tetramethylsilane, Caution:&#160; toxic&#160;</td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;width:216px;">Dimethylsulfoxide-d6</td>
			<td style="width:83px;"></td>
			<td style="width:119px;">185965-50G</td>
			<td>&#160;99.9% D, 1% v/v tetramethylsilane</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">sodium thiosulfate pentahydrate</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">S8503-2.5KG</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">sodium sulfate, anhydrous</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">238597-2.5KG</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">silica gel</td>
			<td style="width:83px;">Fisher Scientific</td>
			<td style="width:119px;">S825-25</td>
			<td>Merck, Grade 60, 230-400 mesh</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">washed sea sand</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">274739-5KG</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">hexane</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">178918-20L</td>
			<td>Caution:&#160; flammable</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">ethyl acetate</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">319902-4L</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">methylene chloride</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">D65100-4L</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">sodium chloride</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">S9888-10KG</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">sodium bicarbonate</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">S6014-2.5KG</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">acetic acid</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">695092-2.5L</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">hydrochloric acid</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">258248-2.5L</td>
			<td>Caution:&#160; Corrosive</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">bromine</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">470864-50G</td>
			<td>&#62;99.99% trace metals basis&#160; Caution:&#160; Corrosive, causes severe burns</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">hydrobromic acid</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">244260-500ML</td>
			<td>48% aqueous, Caution:&#160; Corrosive</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">2,5-dimethoxyphenylacetic acid</td>
			<td style="width:83px;">ChemImpex</td>
			<td style="width:119px;">26909</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">chloroform</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">132950-4L</td>
			<td>Caution:&#160; Toxic</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">tetrahydrofuran</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">360589-4x4L</td>
			<td>Caution:&#160; highly flammable</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">N,N-diisopropylethylamine</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">D125806-500ML</td>
			<td>Caution:&#160; Corrosive</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">triethylamine</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">T0886-1L</td>
			<td>Caution:&#160; Corrosive</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">3 Angstrom molecular sieves</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">208574-1KG</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">calcium hydride</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">213268-100G</td>
			<td>Caution:&#160; Corrosive, reacts violently with water</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">ammonium molybdate</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">431346-50G</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">phosphomolybdic acid</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">221856-100G</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">cerium (IV) sulfate</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">359009-25G</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">1-butanol</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">537993-1L</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">1,4-butanediamine</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">D13208-100G</td>
			<td>Caution:&#160; Corrosive / warm in hot water bath to melt prior to use</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">triphosgene</td>
			<td style="width:83px;">VWR</td>
			<td style="width:119px;">200015-064</td>
			<td>Caution:&#160; Highly Toxic</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">methanol</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">646377-4X4L</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">sodium acetate</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">241245-100G</td>
			<td></td>
		</tr>
		<tr height="44">
			<td height="44" style="height:44px;width:216px;">Dimethylsulfoxide-d6</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">570672-50G</td>
			<td>Anhydrous, 99.9% D</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">sodium hydroxide</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">221465-500G</td>
			<td>Caution:&#160; Corrosive</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">guanidine hydrochloride</td>
			<td style="width:83px;">Sigma-Aldrich</td>
			<td style="width:119px;">G4505-25G</td>
			<td>Caution:&#160; Toxic, Corrosive</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">di-tert-butyl dicarbonate</td>
			<td style="width:83px;">VWR</td>
			<td style="width:119px;">200002-018%</td>
			<td>Caution:&#160; Toxic / may warm in hot water bath to melt prior to use</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">trifluoromethanesulfonic anhydride</td>
			<td style="width:83px;">Fisher Scientific</td>
			<td style="width:119px;">50-206-771</td>
			<td>98%, anhydrous, Caution:&#160; toxic, corrosive, extremely moisture sensitive</td>
		</tr>
	</tbody>
</table>

a direct, early stage guanidinylation protocol for the synthesis of complex aminoguanidine-containing natural products

Die funktionellen Guanidingruppe, zeigte am deutlichsten in der Aminosäure Arginin, einer der fundamentalen Bausteine ​​des Lebens, ist ein wichtiges Strukturelement in vielen komplexen Naturstoffen und Pharmazeutika gefunden. Aufgrund der kontinuierlichen Entdeckung neuer Guanidin haltige Naturprodukte und entwickelt, um kleine Moleküle, die schnelle und effiziente Guanidinylierung Methoden sind von großem Interesse für synthetische und medizinische organischen Chemiker. Da die Nucleophilie und Basizität von Guanidinen nachfolgenden chemischen Umwandlungen beeinflussen können, traditionell, indirekte Guanidinylierung wird in der Regel verfolgt. Indirekte Verfahren verwenden häufig mehrere Schritte Schutz eines latenten Aminvorstufe, wie ein Azid, Phthalimid oder Carbamat beteiligt sind. Durch diese weitschweifigen Methoden zu umgehen und eine direkte Reaktion Guanidinylierung früh in der Synthesesequenz verwendet wird, war es möglich, den linearen endständigen Guanidin enthält Rückgrat der clavatadine A zu schmieden zu realisiereneine kurze und schlanke Synthese dieses potenten Faktor XIa-Inhibitor. In der Praxis wird Guanidin-Hydrochlorid mit einem sorgfältig konstruierten Schutz Array ausgearbeitet, die die Syntheseschritte zu überleben kommen optimiert ist. Bei der Herstellung von clavatadine A, eliminiert direkten Guanidinylierung eines kommerziell erhältlichen Diamins zwei unnötige Schritte von seiner Synthese. Gepaart mit der großen Vielzahl bekannter Guanidin Schutzgruppen, evinces direkte Guanidinylierung eine prägnante und effiziente Praktikabilität inhärent Methoden, die ein Haus in Synthetikers Toolbox finden.

Direkt Guanidinylierung eines kommerziell erhältlichen α, ω-Diamin, gefolgt von der Umsetzung mit Triphosgen, den reaktiven Isocyanat- 8 als dem linearen Abschnitt der clavatadine A (1b) erhalten. Ausbeuten dieses zweistufigen Reaktionsfolge sind immer hoch, 95% oder mehr. Guanidinylierungsreagenz 6 wurde genau wie von Goodman beschrieben. 11,24 Wenn Isocyanat <s...

Watch this Scientific Journal Video about A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products at JoVE.com

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol.

Eine direkte, Early Stage Guanidinylierung Protokoll zur Synthese von komplexen Aminoguanidin haltige Naturprodukte

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important ...

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Research

JoVE Journal

Chemistry

10.5K Aufrufe.  Central Washington University. Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol. 

Serie: A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors

The development of fluorescent indicators represented a revolution for life sciences. Genetically encoded and synthetic fluorophores with sensing abilities allowed the visualization of biologically relevant species with high spatial and temporal resolution. Synthetic dyes are of particular interest thanks to their high tunability and the wide range of measureable analytes. However, these molecules suffer several limitations related to small molecule behavior (poor solubility, difficulties in targeting, often no ratiometric imaging allowed). In this work we introduce the development of dendrimer-based sensors and present a procedure for pH measurement in vitro, in living cells and in vivo. We choose dendrimers as ideal platform for our sensors for their many desirable properties (monodispersity, tunable properties, multivalency) that made them a widely used scaffold for several biomedical devices. The conjugation of fluorescent pH indicators to the dendrimer scaffold led to an enhancement of their sensing performances. In particular dendrimers exhibit reduced cell leakage, improved intracellular targeting and allow ratiometric measurements. These novel sensors were successfully employed to measure pH in living HeLa cells and in vivo in mouse brain.

Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors

Fluorescence sensors are powerful tools in life science. Here we describe a methodology to synthesize and use dendrimer-based fluorescent sensors to measure pH in living cells and in vivo. The dendritic scaffold enhances the properties of conjugated fluorescent dyes leading to improved sensing properties.

Synthesis, Cellular Lieferung und<em&gt; In-vivo-</em&gt; Anwendung der Dendrimer-basierten pH-Sensoren

The development of  fluorescent indicators represented a revolution for life sciences. Genetically  encoded and synthetic fluorophores with sensing ...

Forschung

Chemie

Synthesis of Programmable Main-chain Liquid-crystalline Elastomers Using a Two-stage Thiol-acrylate Reaction

This study presents a novel two-stage thiol-acrylate Michael addition-photopolymerization (TAMAP) reaction to prepare main-chain liquid-crystalline elastomers (LCEs) with facile control over network structure and programming of an aligned monodomain. Tailored LCE networks were synthesized using routine mixing of commercially available starting materials and pouring monomer solutions into molds to cure. An initial polydomain LCE network is formed via a self-limiting thiol-acrylate Michael-addition reaction. Strain-to-failure and glass transition behavior were investigated as a function of crosslinking monomer, pentaerythritol tetrakis(3-mercaptopropionate) (PETMP). An example non-stoichiometric system of 15 mol% PETMP thiol groups and an excess of 15 mol% acrylate groups was used to demonstrate the robust nature of the material. The LCE formed an aligned and transparent monodomain when stretched, with a maximum failure strain over 600%. Stretched LCE samples were able to demonstrate both stress-driven thermal actuation when held under a constant bias stress or the shape-memory effect when stretched and unloaded. A permanently programmed monodomain was achieved via a second-stage photopolymerization reaction of the excess acrylate groups when the sample was in the stretched state. LCE samples were photo-cured and programmed at 100%, 200%, 300%, and 400% strain, with all samples demonstrating over 90% shape fixity when unloaded. The magnitude of total stress-free actuation increased from 35% to 115% with increased programming strain. Overall, the two-stage TAMAP methodology is presented as a powerful tool to prepare main-chain LCE systems and explore structure-property-performance relationships in these fascinating stimuli-sensitive materials.

A novel methodology is presented to synthesize and program main-chain liquid-crystalline elastomers using commercially available starting monomers. A wide range of thermomechanical properties was tailored by adjusting the amount of crosslinker, while the actuation performance was dependent on the amount of applied strain during programming.

Synthese von Programmierbare Hauptkettenflüssigkristalline Elastomere unter Verwendung eines Zwei-Stufen-Thiol-Acrylat-Reaktions

This study presents a novel two-stage thiol-acrylate Michael addition-photopolymerization (TAMAP) reaction to prepare main-chain liquid-crystalline ...

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 &#176;C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

Protokoll für die Synthese von<em&gt; Ortho</em&gt; -trifluoromethoxylated Anilin-Derivate

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

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.

Synthese und Charakterisierung von supramolekularen Kolloid-

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

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation.
We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

This protocol details the important steps required for the bioconjugation of a cysteine containing protein to a maleimide, including reagent purification, reaction conditions, bioconjugate purification and bioconjugate characterization.

Synthese von Protein Biokonjugate<em&gt; über</em&gt; Cystein-maleimid Chemie

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

Synthesis of a Water-soluble Metal&#8211;Organic Complex Array

We demonstrate a method for the synthesis of a water-soluble multimetallic peptidic array containing a predetermined sequence of metal centers such as Ru(II), Pt(II), and Rh(III). The compound, named as a water-soluble metal-organic complex array (WSMOCA), is obtained through 1) the conventional solution-chemistry-based preparation of the corresponding metal complex monomers having a 9-fluorenylmethyloxycarbonyl (Fmoc)-protected amino acid moiety and 2) their sequential coupling together with other water-soluble organic building units on the surface-functionalized polymeric resin by following the procedures originally developed for the solid-phase synthesis of polypeptides, with proper modifications. Traces of reactions determined by mass spectrometric analysis at the representative coupling steps in stage 2 confirm the selective construction of a predetermined sequence of metal centers along with the peptide backbone. The WSMOCA cleaved from the resin at the end of stage 2 has a certain level of solubility in aqueous media dependent on the pH value and/or salt content, which is useful for the purification of the compound.

A potential general method for the synthesis of water-soluble multimetallic peptidic arrays containing a predetermined sequence of metal centers is presented.

Synthese eines wasserlöslichen Metall-organische Komplexe Array

We demonstrate a method for the synthesis of a water-soluble multimetallic peptidic array containing a predetermined sequence of metal centers such as ...

A Rapid Synthesis Method for Au, Pd, and Pt Aerogels Via Direct Solution-Based Reduction

Here, a method to synthesize gold, palladium, and platinum aerogels via a rapid, direct solution-based reduction is presented. The combination of various precursor noble metal ions with reducing agents in a 1:1 (v/v) ratio results in the formation of metal gels within seconds to minutes compared to much longer synthesis times for other techniques such as sol-gel. Conducting the reduction step in a microcentrifuge tube or small volume conical tube facilitates a proposed nucleation, growth, densification, fusion, equilibration model for gel formation, with final gel geometry smaller than the initial reaction volume. This method takes advantage of the vigorous hydrogen gas evolution as a by-product of the reduction step, and as a consequence of reagent concentrations. The solvent accessible specific surface area is determined with both electrochemical impedance spectroscopy and cyclic voltammetry. After rinsing and freeze drying, the resulting aerogel structure is examined with scanning electron microscopy, X-ray diffractometry, and nitrogen gas adsorption. The synthesis method and characterization techniques result in a close correspondence of aerogel ligament sizes. This synthesis method for noble metal aerogels demonstrates that high specific surface area monoliths may be achieved with a rapid and direct reduction approach.

A rapid, direct solution-based reduction synthesis method to obtain Au, Pd, and Pt aerogels is presented.

Eine schnelle Synthese-Methode für Au, Pd und Pt-Aerogelen über lösungsorientierte Direktreduktion

Here, a method to synthesize gold, palladium, and platinum aerogels via a rapid, direct solution-based reduction is presented. The combination of various ...

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 Protokoll für die Synthese von selbst zusammenbauen Polyamin-basierte Peptid Amphiphilen (PPA) und der damit verbundenen Biomaterialien

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

Employing Pressurized Hot Water Extraction (PHWE) to Explore Natural Products Chemistry in the Undergraduate Laboratory

A recently developed pressurized hot water extraction (PHWE) method which utilizes an unmodified household espresso machine to facilitate natural products research has also found applications as an effective teaching tool. Specifically, this technique has been used to introduce second- and third-year undergraduates to aspects of natural products chemistry in the laboratory. In this report, two experiments are presented: the PHWE of eugenol and acetyleugenol from cloves and the PHWE of seselin and (+)-epoxysuberosin from the endemic Australian plant species Correa reflexa. By employing PHWE in these experiments, the crude clove extract, enriched in eugenol and acetyleugenol, was obtained in 4-9% w/w from cloves by second-year undergraduates and seselin and (+)-epoxysuberosin were isolated in yields of up to 1.1% w/w and 0.9% w/w from C. reflexa by third-year students. The former exercise was developed as a replacement for the traditional steam distillation experiment providing an introduction to extraction and separation techniques, while the latter activity featured guided-inquiry teaching methods in an effort to simulate natural products bioprospecting. This primarily derives from the rapid nature of this PHWE technique relative to traditional extraction methods that are often incompatible with the time constraints associated with undergraduate laboratory experiments. This rapid and practical PHWE method can be used to efficiently isolate various classes of organic molecules from a range of plant species. The complementary nature of this technique relative to more traditional methods has also been demonstrated previously.

Employing Pressurized Hot Water Extraction PHWE to Explore Natural Products Chemistry in the Undergraduate Laboratory

Here, we employ a pressurized hot water extraction (PHWE) method, which utilizes an unmodified household espresso machine to introduce undergraduates to natural products chemistry in the laboratory. Two experiments are presented: PHWE of eugenol and acetyleugenol from cloves and PHWE of seselin and (+)-epoxysuberosin from the Australian plant Correa reflexa.

Einsatz von unter Druck stehenden Heißwasserextraktion (PHWE), Naturstoffchemie im Grundstudium Labor zu erkunden

A recently developed pressurized hot water extraction (PHWE) method which utilizes an unmodified household espresso machine to facilitate natural products ...

Automation of a Positron-emission Tomography (PET) Radiotracer Synthesis Protocol for Clinical Production

The development of new positron-emission tomography (PET) tracers is enabling researchers and clinicians to image an increasingly wide array of biological targets and processes. However, the increasing number of different tracers creates challenges for their production at radiopharmacies. While historically it has been practical to dedicate a custom-configured radiosynthesizer and hot cell for the repeated production of each individual tracer, it is becoming necessary to change this workflow. Recent commercial radiosynthesizers based on disposable cassettes/kits for each tracer simplify the production of multiple tracers with one set of equipment by eliminating the need for custom tracer-specific modifications. Furthermore, some of these radiosynthesizers enable the operator to develop and optimize their own synthesis protocols in addition to purchasing commercially-available kits. In this protocol, we describe the general procedure for how the manual synthesis of a new PET tracer can be automated on one of these radiosynthesizers and validated for the production of clinical-grade tracers. As an example, we use the ELIXYS radiosynthesizer, a flexible cassette-based radiochemistry tool that can support both PET tracer development efforts, as well as routine clinical probe manufacturing on the same system, to produce [18F]Clofarabine ([18F]CFA), a PET tracer to measure in vivo deoxycytidine kinase (dCK) enzyme activity. Translating a manual synthesis involves breaking down the synthetic protocol into basic radiochemistry processes that are then translated into intuitive chemistry &#34;unit operations&#34; supported by the synthesizer software. These operations can then rapidly be converted into an automated synthesis program by assembling them using the drag-and-drop interface. After basic testing, the synthesis and purification procedure may require optimization to achieve the desired yield and purity. Once the desired performance is achieved, a validation of the synthesis is carried out to determine its suitability for the production of the radiotracer for clinical use.

Automation of a Positron-emission Tomography PET Radiotracer Synthesis Protocol for Clinical Production

Positron-emission tomography (PET) imaging sites that are involved in multiple early clinical research trials need robust and versatile radiotracer manufacturing capabilities. Using the radiotracer [18F]Clofarabine as an example, we illustrate how to automate the synthesis of a radiotracer using a flexible, cassette-based radiosynthesizer and validate the synthesis for clinical use.

Automatisierung eines Positronen-Emissions-Tomographie (PET) Radiotracer Synthese Protokolls für klinische Herstellung

The development of new positron-emission tomography (PET) tracers is enabling researchers and clinicians to image an increasingly wide array of biological ...

Eine direkte, Early Stage Guanidinylierung Protokoll zur Synthese von komplexen Aminoguanidin haltige Naturprodukte

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