Exploiting binding-site arginines in drug design: Recent examples.

Hong Lin, Juan I Luengo

Journal: Bioorganic & medicinal chemistry letters 2021;30(19):127442

PMID: 32730944

Full Text on Elsevier Science View on PubMed

Abstract

Active or allosteric site arginines can form diverse interactions with ligands including different types of cation-π interactions, H-bond interactions and non-bond, non-canonical interactions. This provides many opportunities for creative structure-based drug design to improve potency, introduce novelty, and modulate MoA (mode of action), and even to achieve selectivity. This digest will use some recent drug targets of interest as examples to illustrate different types of interactions and how these interactions impact on potency, MoA, and selectivity.

Address: Prelude Therapeutics, 200 Powder Mill Road, Wilmington, DE 19803, United States.

DOI: 10.1016/j.bmcl.2020.127442

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MeSH Terms: Allosteric Site, Antineoplastic Agents, Arginine, CREB-Binding Protein, Catalytic Domain, Drug Design, Enzyme Inhibitors, Humans, Ligands, Methionine Adenosyltransferase, Organic Chemicals, Polycomb Repressive Complex 2, Protein Binding