High Throughput Screening of Isomers – IP 1760

Natural products play important roles in drug development.In Particular, ribosomally synthesized and post-translationally modifiedpeptides (RiPPs) present a broad structural diversity, typically restrictingconformational flexibility to allow better target recognition and to increasechemical, physical and proteolytic stability augmenting chemical functionality.For example, lasso peptides are a structural class of RiPPs exhibiting enzymeinhibitory, receptor antagonistic, antimicrobial or antiviral properties.The extraordinary mechanically interlocked topology of lasso peptides,together with their panel of biological activities makes them a promisingscaffold for next generation drug design. However, the discovery and search fornew lasso peptides as potential drug candidates requires high throughputanalytical tools capable of differentiating them from their unthreadedbranched-cyclic topoisomers. FIU inventors have developed methods for theidentification and isolation of isomers, particularly, of RiPPs and otherbiomolecules. These methods allow for the separation and isolation oftopoisomers, such as lasso peptides from the corresponding branched cyclicpeptide isomers, epimers of peptides containing D amino acids, RiPPs positionalisomers based on differences in the tridimensional structure under differentsubstrates and physiological conditions. The methods comprise subjecting asample to a step of ionization comprising a step of metalation, prior to a stepof ion mobility spectrometry (IMS) followed by a step of mass spectrometry(MS). Anne Laure Schmitt Olivier aschmitt@fiu.edu 305-348-5948