Truncated and helix-constrained peptides with high affinity and specificity for the cFos coiled-coil of AP-1.

ABSTRACT: Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i→i+4 helix-inducing constraints, and positioning unnatural

SUBMITTER: Rao T 

PROVIDER: S-EPMC3609778 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature