Efficient new ribozyme mimics: direct mapping of molecular design principles from small molecules to macromolecular, biomimetic catalysts

被引：41

作者：

Putnam, WC ^{[1
]}

Daniher, AT ^{[1
]}

Trawick, BN ^{[1
]}

Bashkin, JK ^{[1
]}

机构：

[1] Washington Univ, Dept Chem, St Louis, MO 63130 USA

来源：

NUCLEIC ACIDS RESEARCH | 2001年 / 29卷 / 10期

关键词：

D O I：

10.1093/nar/29.10.2199

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-phananthroline 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.

引用

页码：2199 / 2204

页数：6

共 41 条

[1] Oligonucleotide-europium complex conjugate designed to cleave the 5′ cap structure of the ICAM-1 transcript potentiates antisense activity in cells [J].