De Novo Design of Helical Electron Transfer Metalloproteins

麦克伦登博士得到了无机化学、生物无机化学和金属有机化学计划的支持，对金属蛋白质中的电子转移进行实验研究。麦克伦登建议使用三螺旋多肽束来探索蛋白质中远程电子耦合的结构关系。在展示了一种允许系统的蛋白质结构变化的合成方法后，可以在已知距离处引入刚性连接的受体/供体部分。本领域的这一进展将允许检查距离依赖于沿螺旋的电子转移。该提案的第二个方面涉及螺旋上氢键位置的衍生化。在螺旋结构或稳定性没有明显扰动的情况下，拟议的修饰将有助于确定氢键路径在电子耦合中的作用。此外，还将研究通过侧链的电子转移以及芳香族残基对电子转移速率的影响。了解金属蛋白中的电子转移一直受到化学家控制蛋白质结构的能力的限制，特别是对氧化还原介导的官能团的访问。通过将已建立的测量技术与系统的蛋白质结构变化方法相结合，可能会克服充分解释这一现象的障碍。

Dr. McLendon is supported by the Inorganic, Bioinorganic and Organometallic Chemistry Program to perform experimental studies of electron transfer in metalloproteins. McLendon has proposed to use three-helix peptide bundles to probe structural relationships in long-range electron coupling in proteins. Having demonstrated a synthetic methodology that allows systematic protein structural variations, rigidly linked acceptor/donor moieties may be introduced at known distances. This advancement in the art will allow the examination of distance dependence upon electron transfer along a helix. A second aspect of the proposal involves derivatization of hydrogen bonding sites on the helix. In the absence of significant perturbations to helix structure or stability, the proposed modification will help determine the role of hydrogen bonding pathways in electronic coupling. Additionally, electron transfer through side chains and the effect of aromatic residues on the rate of electron transfer will be investigated. Understanding electron transfer in metalloproteins has been limited by the ability of chemists to control protein structure, particularly access to redox mediating functional groups. By coupling established measurement techniques with systematic protein structural variation methods, roadblocks to the full elucidation of this phenomenon may be overcome.