COMPOUNDS DESIGNED TO FIT A SITE OF KNOWN STRUCTURE IN HUMAN HAEMOGLOBIN

Abstract

The three‐dimensional coordinates of the atoms in human haemoglobin are known, and there is a specific site in the deoxygenated form of the protein at which 2,3‐diphosphoglycerate (DPG) interacts. Molecular models of this site have been constructed and used to design compounds which should bind to the deoxy conformation and stabilize it. These compounds should thereby promote oxygen liberation, as does DPG. The compounds so designed were found to promote oxygen liberation. Their relative potencies, as assessed by sigmoidal dose‐response curves, are in the predicted sequence. 1976 British Pharmacological Society