MECHANISMS OF ACYL AND PHOSPHORYL TRANSFER

酰基和磷基转移反应是反应的重要组成部分。 生命系统的生物化学。人们对其影响知之甚少 离开基团和亲核性，以及催化基团对反应的影响 这些反应的机理和过渡态。这项工作将 使用各种同位素效应研究来解决这些问题。 初步工作支持从循序渐进的机制向 酰基转移的四面体中间体到协同机理 具有良好离开基团的酯的反应。《公约》的具体目标 本提案中的工作是： 1.获取酰基和酰基过渡态的详细描述 溶液中的磷酰基转移反应和酶反应中的磷酰转移反应。 这些比较将有助于了解酶的作用。 过渡态结构上的催化基团。 2.分析了机制和过渡态结构的差异 产生于离开基团和亲核基团的变化( 碱性或亲核性，以及结合原子的同一性，用于 例如，氧与硫的亲核性)在溶液和酶中 反应。 3.勾画出极限一致与逐步的界限 亲核基团和/或离开基团的性质决定的机理 在溶液中和在酶反应中。 4.确定活化底物是否进行了酶基团转移 通过与未激活的反应相同的机制进行反应，或者如果 不同，就像他们在溶液中所做的那样。

Acyl and phosphoryl group transfer reactions are essential parts of the biochemistry of living systems. Little is known about the influences of leaving group and nucleophile, and the effect of catalytic groups, on the mechanisms and transition states of these reactions. This work will address these questions using a variety of isotope effect studies. Preliminary work supports a change from a stepwise mechanism with a tetrahedral intermediate to a concerted mechanism for acyl transfer reactions of esters with good leaving groups. The specific goals of the work in this proposal are to: 1. Obtain detailed descriptions of the transition states for acyl and phosphoryl transfer reactions in solution and in enzymatic reactions. Comparisons of these will shed light on the effect of the enzymatic catalytic groups on transition state structure. 2. Analyze differences in mechanism and in transition state structure that arise from changes in the leaving group and in the nucleophile (changes in basicity or nucleophilicity, and in identity of the attaching atom, for example, oxygen versus sulfur nucleophiles) in solution and enzymatic reactions. 3. Delineate the boundaries of the limiting concerted vs. stepwise mechanisms as determined by properties of nucleophile and/or leaving group in the solution and in enzymatic reactions. 4. Determine whether activated substrates undergo enzymatic group transfer reactions by the same mechanisms as unactivated ones, or if the mechanisms differ, as they do in solution.