Targeting kinase signaling pathways with constrained peptide scaffolds.

摘要: Kinases are amongst the largest families in human proteome and serve as critical mediators of a myriad cell signaling pathways. Since altered kinase activity is implicated variety pathological diseases, kinases have become prominent class proteins for targeted inhibition. Although numerous small molecule antibody-based inhibitors already received clinical approval, several challenges may still exist with these strategies including resistance, target selection, inhibitor potency vivo profiles. Constrained peptide emerged an alternative strategy Distinct from inhibitors, peptides can provide large binding surface area that allows them to bind shallow protein surfaces rather than defined pockets within structure. By chemical constraints sequence, additional benefits be bestowed onto scaffold such improved affinity selectivity, permeability proteolytic resistance. In this review, we highlight examples diverse chemistries being employed constrain kinase-targeting scaffolds their application modulate well potential implications.