STRUCTURAL DEVELOPMENT OF PROTEIN D-LIGANDS

摘要

A method for developing a D-polypeptide binding to an L-protein target may include identifying a polypeptide target having L-chirality; determining the amino acids of hot spots of a polypeptide ligand having L-chirality, which are characterized by binding interactions with the target L-protein; identification of amino acid side-chain transformations of “hot spots”, which preserve binding interactions with the target; the creation of amino acids inverted "hot spots" with chirality opposite to the chirality of the target; identification of a polypeptide having an inverted chirality compared to a target protein, onto which a combination of amino acids of inverted hot spots can be grafted without significantly altering their interactions with the target. Developed ligands can be processed and converted into D-ligands that bind to the L-protein target.