Review lecture - The imitation of enzymic catalysis

Abstract

This lecture is a report of progress in work that began at Shell Research Ltd’s Milstead Laboratory and has continued at the University of Sussex. I had spent some ten years studying the substrate sterochemistry of enzymes. No one who has done this could fail to be impressed by the stereochemical precision with which enzymes handle their substrates, even when the nature of the product does not exact a stereospecific treatment. It is hard to resist the conclusion that this specificity is an integral and not an incidental feature of the enormous efficiency of enzymes as catalysts. Naturally, like everyone who has worked with enzymes, I form hypotheses about this or that enzymic catalysis; some of these ideas have been testable by stereochemical methods or by various types of isotopic labelling. Further progress can be, and is being, made by the intensive study of particular enzymes, but to someone like myself who is interested in chemical reactions and chemical synthesis it was more attractive to attempt, on the basis of knowledge and conjecture about the nature of enzymic catalysis, to devise synthetic catalysts having the properties of stereospecificity, positional specificity and high efficiency. Without at present presuming to excel or even equal catalytic powers that are thought to have evolved by trial and error over thousands of millions of years, one can, by making the assumption that catalytic activity of this type is not uniquely a property of proteins, substitute the resources of organic chemistry as a whole for the rigours of polypeptide synthesis.