Huang Zupeng, Guan Shuwen, Wang Yongguo, Shi Guannan, Cao Lina, Gao Yuzhou, Dong Zeyuan, Xu Jiayun, Luo Quan, Liu Junqiu
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, People's Republic of China.
J Mater Chem B. 2013 May 7;1(17):2297-2304. doi: 10.1039/c3tb20156b. Epub 2013 Mar 25.
Herein, we report the construction of a novel hydrolase model via self-assembly of a synthetic amphiphilic short peptide (Fmoc-FFH-CONH) into nanotubes. The peptide-based self-assembled nanotubes (PepNTs-His) with imidazolyl groups as the catalytic centers exhibit high catalytic activity for p-nitrophenyl acetate (PNPA) hydrolysis. By replacement of the histidine of Fmoc-FFH-CONH with arginine to produce a structurally similar peptide Fmoc-FFR-CONH, guanidyl groups can be presented in the nanotubes through the co-assembly of these two molecules to stabilize the transition state of the hydrolytic reaction. Therefore significantly improved catalytic activity has been achieved by the reasonable distribution of three dominating catalytic factors: catalytic center, binding site and transition state stabilization to the co-assembled peptide nanotubes (PepNTs-His-Arg). The resulting hydrolase model shows typical saturation kinetics behaviour to that of natural enzymes and the catalytic efficiency of a single catalytic center is 519-fold higher than that without catalysts. As for a nanotube with multi-catalytic centers, a remarkable catalytic efficiency could be achieved with the increase of building blocks. This model suggests that the well ordered and dynamic supramolecular structure is an attractive platform to develop new artificial enzymes to enhance the catalytic activity. Besides, this novel peptide-based material has excellent biocompatibility with human cells and is expected to be applied to organisms as a substitute for natural hydrolases.
在此，我们报道了通过将一种合成两亲性短肽（Fmoc-FFH-CONH）自组装成纳米管来构建新型水解酶模型。以咪唑基为催化中心的基于肽的自组装纳米管（PepNTs-His）对乙酸对硝基苯酯（PNPA）水解表现出高催化活性。通过用精氨酸取代Fmoc-FFH-CONH中的组氨酸以产生结构相似的肽Fmoc-FFR-CONH，胍基可通过这两种分子的共组装出现在纳米管中，以稳定水解反应的过渡态。因此，通过将三个主要催化因素：催化中心、结合位点和过渡态稳定合理分布到共组装肽纳米管（PepNTs-His-Arg）中，实现了催化活性的显著提高。所得的水解酶模型对天然酶表现出典型的饱和动力学行为，单个催化中心的催化效率比无催化剂时高519倍。对于具有多个催化中心的纳米管，随着构建单元的增加可实现显著的催化效率。该模型表明，有序且动态的超分子结构是开发新型人工酶以提高催化活性的有吸引力的平台。此外，这种新型的基于肽的材料与人类细胞具有优异的生物相容性，有望作为天然水解酶的替代品应用于生物体。
