Chemical Sciences Division, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, United States.
J Am Chem Soc. 2021 Feb 3;143(4):2108-2114. doi: 10.1021/jacs.0c12479. Epub 2021 Jan 20.
Supramolecular catalysts emulate the mechanism of enzymes to achieve large rate accelerations and precise selectivity under mild and aqueous conditions. While significant strides have been made in the supramolecular host-promoted synthesis of small molecules, applications of this reactivity to chemoselective and site-selective modification of complex biomolecules remain virtually unexplored. We report here a supramolecular system where coencapsulation of pyridine-borane with a variety of molecules including enones, ketones, aldehydes, oximes, hydrazones, and imines effects efficient reductions under basic aqueous conditions. Upon subjecting unprotected lysine to the host-mediated reductive amination conditions, we observed excellent ε-selectivity, indicating that differential guest binding within the same molecule is possible without sacrificing reactivity. Inspired by the post-translational modification of complex biomolecules by enzymatic systems, we then applied this supramolecular reaction to the site-selective labeling of a single lysine residue in an 11-amino acid peptide chain and human insulin.
超分子催化剂模拟酶的机制，在温和的水相条件下实现大的速率加速和精确的选择性。虽然在超分子主体促进的小分子合成方面已经取得了重大进展，但这种反应性在选择性和位点选择性修饰复杂生物分子方面的应用实际上尚未得到探索。我们在这里报告了一个超分子体系，其中将吡啶-硼烷与各种分子（包括烯酮、酮、醛、肟、腙和亚胺）共包封，在碱性水相条件下可有效还原。当将未保护的赖氨酸置于主体介导的还原胺化条件下时，我们观察到极好的 ε-选择性，表明在不牺牲反应性的情况下，同一分子内的差异客体结合是可能的。受复杂生物分子的酶促修饰的启发，我们然后将这种超分子反应应用于在 11 个氨基酸肽链和人胰岛素中的单个赖氨酸残基的位点选择性标记。
