Synthetic Analogues of Cysteinate-Ligated Metalloenzymes

说明(申请人提供)：腈水合酶(NHase)和超氧化物还原酶(SOR)是一类新的非血红素铁酶，含有与铁配位的半胱氨酸硫化物。它们的功能有很大的不同，从氨酶催化的氰基水合反应到超氧化物还原反应的SOR反应。虽然NHase和SOR的结构已经确定，但关于这两种酶的作用机制仍有许多悬而未决的问题尚未充分解决。在这方面，本提案中描述的研究将集中在对氨酶的反应性进行模拟，以努力了解氰基水解的机理以及多肽酰胺和半胱氨酸硫配体(S)在促进功能方面可能起的作用；确定含氧硫化物是否是氨酶活性所必需的，或者它们是否仅仅是一种人工制品；了解和确定只含氮给电子体的PEL 11-过氧化氢的电子性质和反应性如何因引入硫硫硫而受到影响，并在只有一个配体不同的结构相关的模型体系之间进行直接比较。为了实现这些目标，将合成不同的合成模型化合物，并研究它们的反应活性。

DESCRIPTION (provided by applicant): Nitrile hydratase (NHase) and superoxide reductase (SOR) are a new class of non-heme iron enzymes that contain cysteinate sulfurs coordinated to iron. Their function varies enormously from nitrile hydration, with NHases, to superoxide reduction, with SOR. Although the structures of NHase and SOR have been defined, a number of unresolved questions concerning the mechanisms of action of both enzymes have yet to be adequately addressed. To this regard, the research described in this proposal will focus on modeling the reactivity of NHase in an effort to understand the mechanism of nitrile hydrolysis as well as the role that peptide amides and cysteinate sulfur ligand(s) might play in promoting function; determining whether the oxygenated sulfurs are necessary for NHase activity, or whether they are simply an artifact; understanding and determining how the electronic and reactivity properties of Pel 11-peroxides containing only nitrogen donors are affected by the incorporation of a thiolate sulfur and make direct comparisons between structurally related model systems that differ by only one ligand. To achieve these goals, different synthetic model complexes will be synthesized and their reactivity studied.