Cleavage of a RNA analog containing uridine by a bifunctional dinuclear Zn(II) catalyst

J Inorg Biochem. 2009 Jan;103(1):64-71. doi: 10.1016/j.jinorgbio.2008.09.004. Epub 2008 Sep 19.

Abstract

The macrocyclic ligand, 1,4-bis((1-oxa-4,7,10-triazacyclododecan-7-yl)methyl)benzene (L1) is prepared. L1 binds two Zn(II) ions at neutral pH to form Zn(2)(L1) as studied by using pH-potentiometric titrations. Zn(2)(L1) binds two uridines at pH 7.0, I=0.100M (NaCl) and the mononuclear analog Zn(L2) (L2=1-oxa-4,7,10-triazacyclododecane) binds a single uridine; dissociation constants for both complexes are in the millimolar range. Both complexes promote the cleavage of a simple RNA analog lacking a nucleobase (HpPNP=2-hydroxypropyl-4-nitrophenylphosphate), and a uridine containing RNA analog UpPNP (uridine-3'-4-nitrophenylphosphate). Plots of the first-order rate constant for cleavage of HpPNP as a function of Zn(L2) concentration from 0.5mM to 20.0mM are linear, consistent with weak complexation to substrate K(d)>20mM. In contrast, first-order rate constants for cleavage of UpPNP by Zn(L2) or Zn(2)(L1) over similar concentration ranges exhibit a downward curvature, consistent with the formation of a complex between catalyst and UpPNP. Comparison of second-order rate constants (k(2)=k(cat)/K(d)) shows that the dinuclear complex Zn(2)(L1) is a better catalyst than Zn(L2) for both HpPNP and UpPNP cleavage.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Catalysis
  • Kinetics
  • Ligands
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry*
  • RNA / chemistry*
  • Uridine / chemistry*
  • Zinc / chemistry*

Substances

  • Ligands
  • Organometallic Compounds
  • RNA
  • Zinc
  • Uridine