Structure-based design of D-protein ligands

摘要

Methods of designing a D-polypeptide that binds to an L-target protein may include: identifying a polypeptide target having L-chirality; Determining a hot spot amino acid of a polypeptide ligand having L-chirality having a binding interaction with an L-target protein; Determining the conversion of the side chains of the hotspot amino acids having the target and binding interactions; Generating an inverted hotspot amino acid having an opposite chirality to one of the targets; Identifying a target protein to which a combination of inverted hotspot amino acids can be transplanted and a polypeptide having an inverted chirality without significant alteration of the target and their interaction. The designed ligand can be processed and converted to a D-ligand that binds to the L-target protein.