title: Trinuclear copper(II) complex showing high selectivity for the hydrolysis of 2'-5' over 3'-5' for UpU and 3'-5' over 2'-5' for ApA ribonucleotides.
abstract: The cooperative action of multiple Cu(II) nuclear centers is shown to be effective and selective in the hydrolysis of 2'-5' and 3'-5' ribonucleotides. Reported herein is the specific catalysis by two trinuclear Cu(II) complexes of L3A and L3B. Pseudo first-order kinetic studies reveal that the L3A trinuclear Cu(II) complex effects hydrolysis of Up(2'-5')U with a rate constant of 28 x 10(-)(4) min(-)(1) and Up(3'-5')U with a rate constant of 0.5 x 10(-)(4) min(-)(1). The hydrolyses of Ap(3'-5')A and Ap(2'-5')A proceed with rate constants of 24 x 10(-)(4) min(-)(1) and 0.5 x 10(-)(4) min(-)(1) respectively. The L3A trinuclear Cu(II) complex demonstrates high specificity for Up(2'-5')U and Ap(3'-5')A. Similar studies with the more rigid L3B trinuclear Cu(II) complex shows no selectivity and yields lower rate constants for hydrolysis. The selectivity observed with the L3A ligand is attributed to the geometry of the ligand-bound diribonucleotide which ultimately dictates the proximity of the attacking hydroxyl and the phosphoester to a Cu(II) center for activation and subsequent hydrolysis.
authors.affiliation: Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904 Japan. komiyama@mkoni.rcast.u-tokyo.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Komiyama
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kina
authors.forename: Kazunari
authors.initials: K
authors.lastname: Matsumura
authors.forename: Jun
authors.initials: J
authors.lastname: Sumaoka
authors.forename: Suzanne
authors.initials: S
authors.lastname: Tobey
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Lynch
authors.forename: Eric
authors.initials: E
authors.lastname: Anslyn
mesh_terms: D000227:Adenine Nucleotides / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D015226:Dinucleoside Phosphates / Q000737:chemistry*; D006868:Hydrolysis; D007700:Kinetics; D008024:Ligands; D009942:Organometallic Compounds / Q000737:chemistry*; D012265:Ribonucleotides / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D008024:Ligands; D009942:Organometallic Compounds; D012265:Ribonucleotides; C026519:uridine monophosphate-uridine; D003300:Copper