title: Efficient new ribozyme mimics: direct mapping of molecular design principles from small molecules to macromolecular, biomimetic catalysts.
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.
authors.affiliation: Department of Chemistry, Washington University, St Louis, MO 63130-4899, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Putnam
authors.forename: A T
authors.initials: AT
authors.lastname: Daniher
authors.forename: B N
authors.initials: BN
authors.lastname: Trawick
authors.forename: J K
authors.initials: JK
authors.lastname: Bashkin
mesh_terms: D001483:Base Sequence; D002384:Catalysis; D002413:Cations, Divalent / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D019281:Dimerization; D015195:Drug Design; D007700:Kinetics; D008024:Ligands; D018716:Molecular Mimicry; D015394:Molecular Structure; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015347:RNA Probes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016337:RNA, Catalytic / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D002413:Cations, Divalent; D008024:Ligands; D010618:Phenanthrolines; D011725:Pyridines; D015347:RNA Probes; D016337:RNA, Catalytic; D012313:RNA; D003300:Copper; C002701:neocuproine; C013278:2,2',2''-terpyridine