Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607, United States.
Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, United States.
J Am Chem Soc. 2022 Apr 20;144(15):7001-7009. doi: 10.1021/jacs.2c02146. Epub 2022 Apr 7.
The evolution of proteins from simpler, self-assembled peptides provides a powerful blueprint for the design of complex synthetic materials. Previously, peptide-metal frameworks using short sequences (≤3 residues) have shown great promise as proteomimetic materials that exhibit sophisticated capabilities. However, their development has been hindered due to few variable residues and restricted choice of side-chains that are compatible with metal ions. Herein, we developed a noncovalent strategy featuring π-stacking bipyridyl residues to assemble much longer peptides into crystalline frameworks that tolerate even previously incompatible acidic and basic functionalities and allow an unprecedented level of pore variations. Single-crystal X-ray structures are provided for all variants to guide and validate rational design. These materials exhibit hallmark proteomimetic behaviors such as guest-selective induced fit and assembly of multimetallic units. Significantly, we demonstrate facile optimization of the framework design to substantially increase affinity toward a complex organic molecule.
蛋白质由简单的自组装肽演变而来，为复杂合成材料的设计提供了有力的蓝图。以前，使用短序列（≤3 个残基）的肽-金属框架已显示出作为拟肽材料的巨大潜力，具有复杂的功能。然而，由于可变残基较少且与金属离子兼容的侧链选择有限，它们的发展受到了阻碍。在此，我们开发了一种非共价策略，其特征是π-堆积的联吡啶残基，将更长的肽组装成晶体框架，甚至可以容忍以前不兼容的酸性和碱性官能团，并允许前所未有的孔变化。为所有变体提供单晶 X 射线结构以指导和验证合理的设计。这些材料表现出标志性的拟肽行为，例如客体选择性诱导契合和多金属单元的组装。重要的是，我们证明了框架设计的轻松优化可以大大提高对复杂有机分子的亲和力。
