title: Molecular design of an acid-base cooperative catalyst for RNA cleavage based on a dizinc complex.
abstract: The effects of donor groups of dizinc complexes, formed from a 2:1 mixture of Zn(II) and a dinucleating ligand, on adenylyl(3'-5')adenosine (ApA) cleavage have been studied. Two dinucleating ligands were used: one had two 2-pyridylmethyl and two 2-hydroxyethyl moieties on the 1,3-diamino-2-propanol linker moiety (2), and the other had two 2-pyridylmethyl and two carboxymethyl moieties on the 1,3-diamino-2-propanol linker moiety (3(2-)). The dizinc complex with2 [(Zn(2+))(2)-2] showed higher activities toward ApA cleavage than the dizinc complex using an analogous dinucleating ligand having four 2-pyridylmethyl donor moieties [(Zn(2+))(2)-1] at pH 5-8. The former showed a bell-shaped pH-rate constant profile, whereas the latter showed a sigmoidal pattern. The differences in the pH-rate constant profile are attributable to the various distributions of the monohydroxo-dizinc species, i.e. dideprotonated species, which are responsible for ApA cleavage. The monohydroxo species of (Zn(2+))(2)-2 has two acidic protons, which are not present in the corresponding monohydroxo species of (Zn(2+))(2)-1. The existence of both intracomplex acid (ROH or H(2)O) and base catalysts (RO(-) or OH(-)) in (Zn(2+))(2)-2 can explain its higher activity toward ApA cleavage than that of (Zn(2+))(2)-1. In contrast, (Zn(2+))(2)-3(2-) showed lower activity toward ApA cleavage at pH 7.0, which can be ascribed to the absence of the monohydroxo-dizinc species under these conditions.
authors.affiliation: Department of Applied Chemistry, Faculty of Engineering, Tokyo Polytechnic University, 1583 Iiyama, Atsugi, 243-0297 Kanagawa, Japan. yashiro@chem.t-kougei.ac.jp
authors.forename: Morio
authors.initials: M
authors.lastname: Yashiro
authors.forename: Ryuto
authors.initials: R
authors.lastname: Kawahara
mesh_terms: D000143:Acids / Q000737:chemistry; D002384:Catalysis / Q000187:drug effects; D015195:Drug Design; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011199:Potentiometry; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D015032:Zinc / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000143:Acids; D012313:RNA; D015032:Zinc