Abstract
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).
Benefit
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
Publications
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
Brochure
