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High Throughput Screening of Isomers


Natural 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).


Permits 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 kDa

Market Application

Separation, identification and quantification of isomers for drug design and development


Linear 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:
University: Florida International University
Tech Transfer URL:

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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