RNase T1 mimicking artificial ribonuclease

Nucleic Acids Res. 2007;35(7):2356-67. doi: 10.1093/nar/gkm143. Epub 2007 Mar 27.

Abstract

Recently, artificial ribonucleases (aRNases)--conjugates of oligodeoxyribonucleotides and peptide (LR)(4)-G-amide--were designed and assessed in terms of the activity and specificity of RNA cleavage. The conjugates were shown to cleave RNA at Pyr-A and G-X sequences. Variations of oligonucleotide length and sequence, peptide and linker structure led to the development of conjugates exhibiting G-X cleavage specificity only. The most efficient catalyst is built of nonadeoxyribonucleotide of unique sequence and peptide (LR)(4)-G-NH(2) connected by the linker of three abasic deoxyribonucleotides (conjugate pep-9). Investigation of the cleavage specificity of conjugate pep-9 showed that the compound is the first single-stranded guanine-specific aRNase, which mimics RNase T1. Rate enhancement of RNA cleavage at G-X linkages catalysed by pep-9 is 10(8) compared to non-catalysed reaction, pep-9 cleaves these linkages only 10(5)-fold less efficiently than RNase T1 (k(cat_RNase T1)/k(cat)_(pep)(-9) = 10(5)).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations / chemistry
  • Endoribonucleases / chemistry*
  • Endoribonucleases / metabolism
  • Hydrogen-Ion Concentration
  • Kinetics
  • Oligodeoxyribonucleotides / chemistry*
  • Oligodeoxyribonucleotides / metabolism
  • Peptides / chemistry*
  • Peptides / metabolism
  • RNA / chemistry
  • RNA / metabolism
  • Ribonuclease T1 / chemistry
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Cations
  • Oligodeoxyribonucleotides
  • Pep-9 oligodeoxyribonucleotide-peptide conjugate
  • Peptides
  • RNA
  • Endoribonucleases
  • Ribonuclease T1