<meta charset="utf8"></head><body>LC-MS/MS를 사용한 식물 대사산물에서 트로판 알칼로이드 분류

<ol>
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F., 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=MS/MS-based+molecular+networking:+An+efficient+approach+for+natural+products+dereplication.">MS/MS-based molecular networking: An efficient approach for natural products dereplication.</a> Molecules. 28, 157 (2023).</li><li>Du, N., Zhou, W., Jin, H., Liu, Y., Zhou, H., Liang, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+tropane+and+cinnamamide+alkaloids+from+Scopolia+tangutica+by+high-performance+liquid+chromatography+with+quadrupole+time-of-flight+tandem+mass+spectrometry.">Characterization of tropane and cinnamamide alkaloids from Scopolia tangutica by high-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry.</a> J Sep Sci. 42 (6), 1163-1173 (2019).</li><li>Agnes, S. A., 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=Implementation+of+a+MS/MS+database+for+isoquinoline+alkaloids+and+other+annonaceous+metabolites.">Implementation of a MS/MS database for isoquinoline alkaloids and other annonaceous metabolites.</a> Sci Data. 9 (1), 270 (2022).</li><li>Sixto, A., P&#233;rez-Parada, A., Niell, S., Heinzen, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=GC-MS+and+LC-MS/MS+workflows+for+the+identification+and+quantitation+of+pyrrolizidine+alkaloids+in+plant+extracts,+a+case+study:+Echium+plantagineum.">GC-MS and LC-MS/MS workflows for the identification and quantitation of pyrrolizidine alkaloids in plant extracts, a case study: Echium plantagineum.</a> Rev Bras Farmacog. 29 (4), 500-503 (2019).</li><li>Wang, H., Xu, X., Wang, X., Guo, W., Jia, W., Zhang, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+analytical+strategy+for+discovering+structural+analogues+of+alkaloids+in+plant+food+using+characteristic+structural+fragments+extraction+by+high+resolution+orbitrap+mass+spectrometry.">An analytical strategy for discovering structural analogues of alkaloids in plant food using characteristic structural fragments extraction by high resolution orbitrap mass spectrometry.</a> LWT- Sci Technol. 154, 112329 (2022).</li><li>Parks, H. 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=Redirecting+tropane+alkaloid+metabolism+reveals+pyrrolidine+alkaloid+diversity+in+Atropa+belladonna.">Redirecting tropane alkaloid metabolism reveals pyrrolidine alkaloid diversity in Atropa belladonna.</a> New Phytol. 237 (5), 1810-1825 (2023).</li><li>. MassBank of North America Available from: <a target="_blank" href="https://mona.fiehnlab.ucdavis.edu">https://mona.fiehnlab.ucdavis.edu</a> (2024)</li><li>Maier, I., 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=Fluorodaturatin+und+Homofluorodaturatin+-+zwei+neue+&#946;-carbolinderivate+in+Samen+von+Datura+stramonium+L.+var.+stramonium.">Fluorodaturatin und Homofluorodaturatin - zwei neue &#946;-carbolinderivate in Samen von Datura stramonium L. var. stramonium.</a> Monatsh Chem. 112, 1425-1439 (1981).</li><li>Jennett-Siems, 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=Chemotaxonomy+of+the+pantropical+genus+Merremia+(Convolvulaceae)+based+on+the+distribution+of+tropane+alkaloids.">Chemotaxonomy of the pantropical genus Merremia (Convolvulaceae) based on the distribution of tropane alkaloids.</a> Phytochemistry. 66, 1448-1464 (2005).</li><li>Kohnen, K. L., Sezgin, S., Spiteller, M., Hagels, H., Kayser, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Localization+and+organization+of+scopolamine+biosynthesis+in+Duboisia+myoporoides+R.">Localization and organization of scopolamine biosynthesis in Duboisia myoporoides R.</a> Br. Plant Cell Physiol. 59 (1), 107-118 (2018).</li><li>Guan, 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=Full+collision+energy+ramp-MS2+spectrum+in+structural+analysis+relying+on+MS/MS.">Full collision energy ramp-MS2 spectrum in structural analysis relying on MS/MS.</a> Anal Chem. 93 (46), 15381-15389 (2021).</li><li>Al Balkhi, M. H., Schlitz, S., Lesur, D., Lanoue, A., Wadouachi, M., Boitel-Conti, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Norlittorine+and+norhyoscyamine+identified+as+products+of+littorine+and+hyoscyamine+metabolism+by+13C-labeling+in+Datura+innoxia+hairy+roots.">Norlittorine and norhyoscyamine identified as products of littorine and hyoscyamine metabolism by 13C-labeling in Datura innoxia hairy roots.</a> Phytochemistry. 74, 105-114 (2012).</li><li>Sumner, L. W., 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=Proposed+minimum+reporting+standards+for+chemical+analysis.">Proposed minimum reporting standards for chemical analysis.</a> Metabolomics. 3, 211-221 (2007).</li><li>Gambaro, V., Labbe, C., Castillo, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Angeloyl,+Tigloyl+and+Senecioyloxytropane+Alkaloids+from+Schizanthus+hookerii.">Angeloyl, Tigloyl and Senecioyloxytropane Alkaloids from Schizanthus hookerii.</a> Phytochemistry. 22 (8), 1838-1839 (1983).</li><li>Christen, P., Cretton, S., Humam, M., Bieri, S., Mu&#241;oz, O., Joseph-Nathan, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemistry+and+biological+activity+of+alkaloids+from+the+genus+Schizanthus.">Chemistry and biological activity of alkaloids from the genus Schizanthus.</a> Phytochem Rev. 19, 615-641 (2020).</li><li>Lounasmaa, M., Tamminen, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Tropane+Alkaloids.">The Tropane Alkaloids.</a> The Alkaloids: Chemistry and Pharmacology. , (1993).</li></ol>

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Acetonitrile, For UHPLC, suitable for mass spectometry</td>
			<td>Sigma-Aldrich</td>
			<td>900667</td>
			<td>HPLC solvent</td>
		</tr>
		<tr>
			<td>Argon gas</td>
			<td>AirGas</td>
			<td>AR UHP300</td>
			<td>CID gas</td>
		</tr>
		<tr>
			<td>Formic acid, 99% for analysis</td>
			<td>Thermo Scientific</td>
			<td>AC270480010</td>
			<td>HPLC additive</td>
		</tr>
		<tr>
			<td>Guard column holder</td>
			<td>Restek</td>
			<td>25812</td>
			<td></td>
		</tr>
		<tr>
			<td>HPLC, Shimadzu LC-2030C 3D Plus</td>
			<td>Shimadzu</td>
			<td>228-65802-58</td>
			<td>HPLC column</td>
		</tr>
		<tr>
			<td>LCMS, Shimdazu LCMS-8045</td>
			<td>Shimadzu</td>
			<td>225-31800-44</td>
			<td>Mass spectrometer; we ran LabSolutions software, which is standard for Shimadzu instruments</td>
		</tr>
		<tr>
			<td>Liquid nitrogen</td>
			<td>AirGas</td>
			<td>NI 180LT22</td>
			<td></td>
		</tr>
		<tr>
			<td>Methanol, for HPLC/UHPLC/LCMS</td>
			<td>VWR</td>
			<td>BDH 85800.400</td>
			<td>For making extraction solvent</td>
		</tr>
		<tr>
			<td>Microcentrifuge&#160;</td>
			<td>VWR</td>
			<td>2400-37</td>
			<td></td>
		</tr>
		<tr>
			<td>Microcentrifuge tubes, 1.5 mL</td>
			<td>Fisher Scientific</td>
			<td>05-408-129</td>
			<td></td>
		</tr>
		<tr>
			<td>Mortar&#160;</td>
			<td>Fisher Scientific</td>
			<td>FB961C</td>
			<td>For grinding plant tissues</td>
		</tr>
		<tr>
			<td>Pestle</td>
			<td>Fisher Scientific</td>
			<td>FB961M</td>
			<td>For grinding plant tissues</td>
		</tr>
		<tr>
			<td>Pipette 1000 mL</td>
			<td>Gilson&#160;</td>
			<td>F144059M</td>
			<td></td>
		</tr>
		<tr>
			<td>Pipette tip 1000 mL</td>
			<td>Fisher scientific</td>
			<td>02-707-404</td>
			<td></td>
		</tr>
		<tr>
			<td>Plant tissues</td>
			<td>Various sources</td>
			<td>N/A</td>
			<td>Can be anything wild or cultivated</td>
		</tr>
		<tr>
			<td>Polypropylene conical tubes, 15 mL</td>
			<td>Fisher Scientific</td>
			<td>05-539-4</td>
			<td></td>
		</tr>
		<tr>
			<td>Polystyrene cooler</td>
			<td>ULINE</td>
			<td>S-18312</td>
			<td>The type of coolers that reagents for molecular biology are shipped in would be appropriate</td>
		</tr>
		<tr>
			<td>Roc C18 3 &#181;m, 100 mm x 4.6 mm</td>
			<td>Restek</td>
			<td>9534315</td>
			<td>HPLC column</td>
		</tr>
		<tr>
			<td>Roc C18, 10 mm x 4 mm</td>
			<td>Restek</td>
			<td>953450210</td>
			<td>Guard column</td>
		</tr>
		<tr>
			<td>Rocking shaker</td>
			<td>Themo Scientific</td>
			<td>11-676-680</td>
			<td></td>
		</tr>
		<tr>
			<td>Screw thread vial convenience kit (9 mm)</td>
			<td>Fisher scientific</td>
			<td>13-622-190</td>
			<td>LCMS autosampler vials</td>
		</tr>
		<tr>
			<td>Syringe, 3 mL</td>
			<td>Fisher Scientific</td>
			<td>03-377-27</td>
			<td></td>
		</tr>
		<tr>
			<td>Syringe filter 0.45 &#181;m&#160;</td>
			<td>Avantor/VWR</td>
			<td>76479-008</td>
			<td></td>
		</tr>
		<tr>
			<td>Water, for use in liquid chromatography and mass spectrometry</td>
			<td>JT Baker</td>
			<td>9831-03</td>
			<td>For making extraction solvent</td>
		</tr>
		<tr>
			<td>Water solution, contains 0.1% v/v formic acid, For UHPLC, suitable for mass spectometry</td>
			<td>Sigma-Aldrich</td>
			<td>900687-1L</td>
			<td>HPLC solvent</td>
		</tr>
	</tbody>
</table>

applications of liquid-chromatography tandem mass spectrometry in natural products research: tropane alkaloids as a case study

Although fully synthetic molecules have become more prominent in drug discovery in recent decades, nearly two-thirds of all approved drugs from the last 39 years are natural products or natural-product-inspired,1,2&#160;underscoring the continued importance of natural products research. Alkaloids, certain nitrogen-containing natural products, are especially prized for their medicinal properties. Tropane alkaloids (TAs) containing the [3.2.1.]-bicyclic nitrogen-containing system, are produced mostly by plants in the Solanaceae (nightshade), Erythroxylaceae, and Convolvulaceae families. Examples include atropine, scopolamine, and cocaine; multiple semi-synthetic or synthetic tropanes are also used clinically3. TAs and their derivatives are used to treat many conditions3,4 and several of these drugs appear on the WHO&#39;s 2023 List of Essential Medicines5. Because of their potent activities, TAs are also used recreationally (as stimulants or deliriants) and can cause poisoning upon ingestion of plants (or preparations) that contain them6,7. TAs are undesirable in human and animal food8 and can taint teas, spices, grains, honey, and herbal supplements9,10.&#160;Because of both their medicinal promise and ability to poison, analytical methods that can aid in the discovery of new TAs (and identification of known TAs) are useful.
In tandem mass spectrometry (MS/MS), &#34;mass filters&#34; (e.g., quadrupoles, time-of-flight tubes) are coupled together physically (&#34;in-space&#34;), or an instrument employs additional &#34;in-time&#34; reaction/separation steps. In-space MS/MS uses different modes to select and fragment different ions at the different mass filters (e.g., the quadrupoles of a triple-quadrupole or QQQ instrument). These different modes can be used to determine which specific fragments are made by a given ion (product ion scan), which ions in a sample yield certain fragments (precursor ion scan or PrIS) or undergo losses of a characteristic mass (neutral loss scan or NLS), or which specific compounds possess which specific fragments (multiple reaction monitoring). MS/MS, therefore, provides fragments that are useful for proposing structures for new compounds or confirming an existing compound&#39;s presence. MS/MS is increasingly used in the drug discovery, natural products chemistry, and metabolomics fields11,12,&#160;and has been used to profile alkaloid-containing species (for phytochemical characterization or chemotaxonomic analysis) and to detect and quantify specific alkaloids in food or medicinal plants10,13,14,15,16.
Despite the many mass spectrometry techniques available, there are challenges in finding new alkaloids. In addition to finding a candidate organism to screen, a full structural confirmation of an alkaloid is an arduous process that may include many different analytical techniques. Additionally, researchers could isolate a compound that is already known, wasting labor, time, and resources. This is especially difficult for TAs, where hundreds, if not thousands of TAs, many of which are isomeric with one another, are reported. The process of &#34;identifying the knowns and distinguishing them from the unknowns&#34; is known as dereplication. Databases of the retention times (r.t.s) and mass fragments of different TAs and other compounds are published to aid with this process17,18.&#160;Nonetheless, dereplication is laborious; merely annotating (i.e., assigning putative structures to) the alkaloids in a sample&#39;s entire LC-MS/MS chromatogram is time-consuming. Recently, both molecular networking19,20 and manual dereplication18,21,22 have been used for benzylisoquinoline, monoterpene indole, and tropane alkaloids, and PrISs have been used for &#34;structural filtering&#34; of spectra to identify pyrrolizidine and solanine-type alkaloids23,24.&#160;There are no specific methods or workflows available for rapid LC-MS/MS-based dereplication of TA-containing samples, however, even though TAs possess common, easily-identifiable fragments (Figure 1). The method described here uses a combination of data-dependent (DD) product ion scans, PrISs, and NLSs to annotate and classify TA structures in plants based on both the distinct fragmentation patterns for mono-, di-, and trisubstituted tropanes (Figure 1A) and the losses of common ester groups found in these alkaloids (Figure 1B). The study organisms are several species in the nightshade genus Datura. A rich source of diverse TAs, Datura has been used&#160;throughout the world&#39;s history for medicinal and cultural purposes17- and is a challenging matrix to dereplicate because of its numerous, structurally similar TAs, providing us with appealing samples upon which to test our method.

<meta charset="utf8"></head><body>저자 스포트라이트: Discovering New Alkaloids in Plants with Advanced Mass Spectrometry Techniques (고급 질량 분석 기법을 사용한 식물의 새로운 알칼로이드 발견)

천연 제품 연구에서 액체 크로마토그래피 탠덤 질량분석법의 응용 분야: 사례 연구로서의 트로판 알칼로이드

In the simplest form of our research, we are trying to discover new molecules in plants. Plants are chemically complex, and some of these chemicals may be medicinally useful. We're especially interested in finding new alkaloids, which are certain molecules that contain nitrogen.Recently, we have so many new different alkaloid instruments and techniques available, so people discover more and more new molecules every day. With these instruments, we can answer questions like what chemicals are present, when are they present, and what part of the plant can they be found? Mass spectrometry as an analytical technique has really improved over the past 50 years.Instruments are more powerful, less expensive, and have higher resolution. And these techniques allow us to not only identify more plant molecules like alkaloids but also be more sure in our identification. This method is fast and sensitive.We were able to collect a full set of data on nightshade plants containing many tropane alkaloids in 60 to 90 minutes, and assign proposed structures to even though low upon those alkaloids. We're very interested in developing tandem mass spectrometry-based filtering methods for other classes of alkaloids and using methods like these to study how plant chemistry differs between different species, different plant parts, and different growth stages.

Read this Scientific Article Protocol about Applications of Liquid Chromatography-Tandem Mass Spectrometry in Natural Products Research: Tropane Alkaloids as a Case Study at JoVE.com

Although many drugs utilized today are synthetic in origin, natural products still provide a rich source of novel chemical diversity and bioactivity, and ...

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Applications of Liquid-Chromatography Tandem Mass Spectrometry in Natural Products Research: Tropane Alkaloids as a Case Study

370 조회수.  Northern Michigan University. 우리 연구의 가장 간단한 형태로, 우리는 식물에서 새로운 분자를 발견하려고 노력하고 있습니다. 식물은 화학적으로 복잡하며 이러한 화학 물질 중 일부는 의학적으로 유용할 수 있습니다. 우리는 특히 질소를 포함하는 특정 분자인 새로운 알칼로이드를 찾는 데 관심이 있습니다.최근에는 새로운 알칼로이드 기기와 기술을 사용할 수 있게 되?...