Targeting kinases with constrained peptide scaffolds

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 constr

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When Counting Electrons Matter: Tuning Noncovalent Interactions with Aromaticity

Aromaticity and hydrogen bonding are traditionally considered to be largely separate ideas in chemistry. We find however, that just as a change in aromaticity can enhance chemical reactivity (e.g., consider the effect of an aromatic transition state on a cycloaddition reaction)—a change in aromaticity can perturb the strengths of hydrogen bonding interactions (and even more exotic types of noncovalent interactions).

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