Design of peptide-acridine mimics of ribonuclease activity Academic Article uri icon

Overview

MeSH Major

  • Acridines
  • Oligopeptides
  • RNA
  • Ribonucleases

abstract

  • A series of peptide-acridine conjugates was designed and synthesized, based on three features of the proposed catalytic mechanism of RNase A: 2'-proton abstraction by His-12, proton donation to the leaving 5'-oxygen by His-119, and stabilization of the pentacoordinated phosphorous transition state by Lys-41. The substrate binding capability of RNase A was mimicked by the intercalator, acridine. Lysine served as a linker between acridine and the catalytic tripeptide. Cleavage of target RNA was monitored by agarose gel electrophoresis and by gel-permeation chromatography. The carboxyl-amidated conjugates HGHK(Acr)-NH2, HPHK(Acr)-NH2, and GGHK(Acr)-NH2 (where Acr indicates 2-methyl-9-acridinemethylene) all had similar hydrolytic activity. The catalytic mechanism most likely involved only the abstraction of the 2'-proton and stabilization of the transition state. These RNase mimics utilized rRNA and single-stranded RNA but not double-stranded RNA and tRNA as substrates.

publication date

  • December 1992

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC49656

PubMed ID

  • 1379732

Additional Document Info

start page

  • 7114

end page

  • 8

volume

  • 89

number

  • 15