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High Throughput Screening of Isomers | |
Description: | AbstractNatural products play important roles in drug development. In Particular, ribosomally synthesized and post-translationally modified peptides (RiPPs) present a broad structural diversity, typically restricting conformational flexibility to allow better target recognition and to increase chemical, physical and proteolytic stability augmenting chemical functionality. For example, lasso peptides are a structural class of RiPPs exhibiting enzyme inhibitory, receptor antagonistic, antimicrobial or antiviral properties. The extraordinary mechanically interlocked topology of lasso peptides, together with their panel of biological activities makes them a promising scaffold for next generation drug design. However, the discovery and search for new lasso peptides as potential drug candidates requires high throughput analytical tools capable of differentiating them from their unthreaded branched-cyclic topoisomers. FIU inventors have developed methods for the identification and isolation of isomers, particularly, of RiPPs and other biomolecules. These methods allow for the separation and isolation of topoisomers, such as lasso peptides from the corresponding branched cyclic peptide isomers, epimers of peptides containing D amino acids, RiPPs positional isomers based on differences in the tridimensional structure under different substrates and physiological conditions. The methods comprise subjecting a sample to a step of ionization comprising a step of metalation, prior to a step of ion mobility spectrometry (IMS) followed by a step of mass spectrometry (MS).BenefitPermits the direct analysis of complex biological samples and the identification of isomers of biomolecules, such as polypeptides and proteinsSeparates isomers having a molecular weight between 400 Da to 1000 kDaMarket ApplicationSeparation, identification and quantification of isomers for drug design and developmentPublicationsLinear and Differential Ion Mobility Separations of Middle-Down Proteoforms, Anal. Chem. 2018, 90, 4, 2918–2925Fast and Effective Ion Mobility–Mass Spectrometry Separation of d-Amino-Acid-Containing Peptides Anal. Chem. 2017, 89, 21, 11787–11794Identification of Lasso Peptide Topologies Using Native Nanoelectrospray Ionization-Trapped Ion Mobility Spectrometry–Mass Spectrometry, Anal. Chem. 2018, 90, 8, 5139–5146 |
Research Terms: |
Life Sciences > Biology Physical Sciences > Chemistry |
Keywords: | Biosciences/Chemistry; |
Technology Inventors: |
Francisco Alberto Fernandez Lima Kevin Jeanne Dit Fouque |
Technology Information URL: | https://fau.flintbox.com/technologies/2d6c4264-6333-4bcb-8bae-2d56bd7e1ddf |
University: | Florida International University |
Tech Transfer URL: | https://research.fiu.edu/innovation-and-economic-dev/ |
Associated Patents
Patent Name: | No Patent Title |
Patent Number: | US 10,386,372 |
Patent Status: | Issued |
Patent Record: |
View full record at google patents View full record at United States Patent and Trademark Office |
Patent Inventors: |
Francisco Alberto Fernandez Lima Kevin Jeanne Dit Fouque |
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