1994 Syntex Award Lecture: Anionic Electrophiles, Protein Modification, and Artificial Blood

Abstract

Monomethyl esters of acyl phosphates (mixed anhydrides of carboxylic and phosphoric acids) are being developed as site-directed acylating agents for amino groups in proteins. In an illustrative application, these anionic materials are shown to bind to a positively charged region of hemoglobin where they convert amino groups to amides. Bifunctional acyl methyl phosphates cross-link hemoglobin to give a variety of products, some of which have the oxygen-binding properties anticipated for materials that can serve as an alternative to red cells in transfusions. Higher yields of desired products result from the use of a trifunctional analogue. Kinetic patterns of the reactions of a series of alkyl amines and methyl aroyl phosphates indicate that the transition state for formation of the amide involves almost complete development of positive charge on nitrogen.