高效新型核酶模拟物：从小分子到大分子仿生催化剂分子设计原理的直接映射
Efficient new ribozyme mimics: direct mapping of molecular design principles from small molecules to macromolecular, biomimetic catalysts.
作者信息
Putnam W C, Daniher A T, Trawick B N, Bashkin J K
机构信息
Department of Chemistry, Washington University, St Louis, MO 63130-4899, USA.
出版信息
Nucleic Acids Res. 2001 May 15;29(10):2199-204. doi: 10.1093/nar/29.10.2199.
Abstract
Dramatic improvements in ribozyme mimics have been achieved by employing the principles of small molecule catalysis to the design of macromolecular, biomimetic reagents. Ribozyme mimics derived from the ligand 2,9-dimethylphenanthroline (neocuproine) show at least 30-fold improvements in efficiency at sequence-specific RNA cleavage when compared with analogous o-phenanthroline- and terpyridine-derived reagents. The suppression of hydroxide-bridged dimers and the greater activation of coordinated water by Cu(II) neocuproine (compared with the o-phenanthroline and terpyridine complexes) better allow Cu(II) to reach its catalytic potential as a biomimetic RNA cleavage agent. This work demonstrates the direct mapping of molecular design principles from small-molecule cleavage to macromolecular cleavage events, generating enhanced biomimetic, sequence-specific RNA cleavage agents.
摘要
通过将小分子催化原理应用于大分子仿生试剂的设计，核酶模拟物已取得了显著进展。与类似的邻菲罗啉和三联吡啶衍生试剂相比，源自配体2,9-二甲基菲咯啉（新铜试剂）的核酶模拟物在序列特异性RNA切割效率上至少提高了30倍。与邻菲罗啉和三联吡啶配合物相比，新铜试剂（Cu(II)）对氢氧化物桥联二聚体的抑制以及对配位水的更大活化作用，使Cu(II)作为仿生RNA切割剂能更好地发挥其催化潜力。这项工作展示了从小分子切割到大分子切割事件的分子设计原理的直接映射，产生了增强的仿生、序列特异性RNA切割剂。
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