Transition State Analysis Using Multiple Kinetic Isotope Effects: Mechanisms of Enzymatic and Non-enzymatic Glycoside Hydrolysis and Transfer

Abstract

Publisher Summary This chapter attempts to provide a summary of the use of transition state (TS) analysis in understanding glycoside chemistry, as well as an overview of recent developments in the field. TS analysis is only one tool in any comprehensive analysis of reactivity and catalysis. It addresses both the principles and practice of TS analysis and recent advances in the understanding of hydrolysis and glycosyl transfer reactions of N- and O-glycosides. TS analysis means the use of multiple kinetic isotope effects to define transition states in atomic detail. It has been possible to determine the structure of the TS, a species that exists for less than a single bond vibration, with accuracy that rivals that of X-ray crystallography of stable molecules. These studies have elucidated both the chemistry of these reactions and the strategies used by enzymes to promote catalysis. The use of TS analysis to build quantitative, atomic resolution transition state models is still a relatively new technique. The chapter describes the techniques of TS analysis as applied to glycoside chemistry and recent results that have emerged from these studies.