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

Dramatic improvements in ribozyme mimics have been achieved by employing th e principles of small molecule catalysis to the design of macromolecular, b iomimetic reagents. Ribozyme mimics derived from the ligand 2,9-dimethylphe nanthroline (neocuproine) show at least 30-fold improvements in efficiency at sequence-specific RNA cleavage when compared with analogous o-phenanthro line- and terpyridine-derived reagents. The suppression of hydroxide-bridge d dimers and the greater activation of coordinated water by Cu(II) neocupro ine (compared with the o-phananthroline and terpyridine complexes) better a llow Cu(II) to reach its catalytic potential as a biomimetic RNA cleavage a gent. This work demonstrates the direct mapping of molecular design princip les from small-molecule cleavage to macromolecular cleavage events, generat ing enhanced biomimetic, sequence-specific RNA cleavage agents.