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. 1992 Aug 1;89(15):7114–7118. doi: 10.1073/pnas.89.15.7114

Design of peptide-acridine mimics of ribonuclease activity.

C H Tung 1, Z Wei 1, M J Leibowitz 1, S Stein 1
PMCID: PMC49656  PMID: 1379732

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.

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Selected References

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