Laungani Andy C, Slattery John M, Krossing Ingo, Breit Bernhard
Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
Chemistry. 2008;14(15):4488-502. doi: 10.1002/chem.200800359.
The principles of protein structure design, molecular recognition, and supramolecular and combinatorial chemistry have been applied to develop a convergent metal-ion-assisted self-assembly approach that is a very simple and effective method for the de novo design and the construction of topologically predetermined antiparallel beta-sheet structures and self-assembled catalysts. A new concept of in situ generation of bidentate P-ligands for transition-metal catalysis, in which two complementary, monodentate, peptide-based ligands are brought together by employing peptide secondary structure motif as constructing tool to direct the self-assembly process, is achieved through formation of stable beta-sheet motifs and subsequent control of selectivity. The supramolecular structures were studied by (1)H, (31)P, and (13)C NMR spectroscopy, ESI mass spectrometry, X-ray structure analysis, and theoretical calculations. Our initial catalysis results confirm the close relationship between the self-assembled sheet conformations and the catalytic activity of these metallopeptides in the asymmetric rhodium-catalyzed hydroformylation. Good catalyst activity and moderate enantioselectivity were observed for the selected combination of catalyst and substrate, but most importantly the concept of this new methodology was successfully proven. This work presents a perspective interface between protein design and supramolecular catalysis for the design of beta-sheet mimetics and screening of libraries of self-organizing supramolecular catalysts.
蛋白质结构设计、分子识别以及超分子和组合化学的原理已被应用于开发一种收敛的金属离子辅助自组装方法，这是一种从头设计和构建拓扑预定的反平行β-折叠结构及自组装催化剂的非常简单有效的方法。通过形成稳定的β-折叠基序并随后控制选择性，实现了一种用于过渡金属催化的双齿P-配体原位生成的新概念，其中通过使用肽二级结构基序作为构建工具将两个互补的单齿肽基配体聚集在一起，以指导自组装过程。通过（1）H、（31）P和（13）C NMR光谱、ESI质谱、X射线结构分析和理论计算对超分子结构进行了研究。我们最初的催化结果证实了自组装片层构象与这些金属肽在不对称铑催化的氢甲酰化反应中的催化活性之间的密切关系。对于选定的催化剂和底物组合，观察到了良好的催化剂活性和适度的对映选择性，但最重要的是成功证明了这种新方法的概念。这项工作展示了蛋白质设计与超分子催化之间的一个视角界面，用于β-折叠模拟物的设计和自组织超分子催化剂库的筛选。
