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Targeting kinases with constrained peptide scaffolds

Prof. Eileen Kennedy
Prof. Eileen Kennedy
College of Pharmacy
University of Georgia
Chemistry Building, Room 400
Organic Seminar

Misregulation of kinases is implicated in a myriad of diseases and significant efforts have been put forth towards the development of targeted kinase inhibitors.  However, many issues remain with current therapeutic strategies including specificity and inhibitor resistance.  As an alternative approach for targeted inhibition, we have developed inhibitors targeting protein-protein interfaces (PPIs) that bind evolutionarily conserved structural features for a kinase of interest.  These peptide-based inhibitors are chemically constrained to present a large binding surface area while also possessing properties of small molecules.  These constrained peptides demonstrate a unique strategy for allosteric regulation and broaden the possibility of targeting unique protein surfaces that may not be accessible using a small molecule approach.  In addition, we have used this approach to perturb spatiotemporal kinase regulation in the context of live cells.

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