Covalently attached oligodeoxyribonucleotides induce RNase activity of a short peptide and modulate its base specificity

Nucleic Acids Res. 2004 Mar 26;32(6):1928-36. doi: 10.1093/nar/gkh514. Print 2004.

Abstract

New artificial ribonucleases, conjugates of short oligodeoxyribonucleotides with peptides containing alternating arginine and leucine, were synthesized and characterized in terms of their catalytic activity and specificity of RNA cleavage. The conjugates efficiently cleave different RNAs within single-stranded regions. Depending on the sequence and length of the oligonucleotide, the conjugates display either G-X>>Pyr-A or Pyr-A>>G-X cleavage specificity. Preferential RNA cleavage at G-X phosphodiester bonds was observed for conjugate NH2-Gly-[ArgLeu]4-CCAAACA. The conjugates function as true catalysts, exhibiting reaction turnover up to 175 for 24 h. Our data show that in the conjugate the oligonucleotide plays the role of a factor which provides an 'active' conformation of the peptide via intramolecular interactions, and that it is the peptide residue itself which is responsible for substrate affinity and catalysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Arginine / chemistry
  • Base Sequence
  • Enzyme Activation
  • HIV-1 / genetics
  • Kinetics
  • Leucine / chemistry
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / chemistry*
  • Oligopeptides / chemistry*
  • Oligopeptides / metabolism*
  • RNA / chemistry
  • RNA / metabolism
  • RNA, Viral / chemistry
  • RNA, Viral / metabolism
  • Ribonucleases / chemistry*
  • Ribonucleases / metabolism*
  • Substrate Specificity

Substances

  • Oligodeoxyribonucleotides
  • Oligopeptides
  • RNA, Viral
  • RNA
  • Arginine
  • Ribonucleases
  • Leucine