Molecular recognition between oligopeptides and nucleic acids: Dna binding specificity of a series of bis netropsin analogues deduced from footprinting analysis

Koren L. Kissinger, James C. Dabrowiak, J. William Lown

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

A series of tether-linked bis netropsins have been synthesized in order to assess the phasing problem, which arises because of the lack of dimensional correspondence between oligopeptides and oligonucleotides in DNA binding characteristics. The consequences of incorporating variable- length flexible and rigid tethers [poly(methylene), Z and E ethylene, m- and p-phenylene] between the two netropsin-like moieties on the DNA binding properties were assessed by DNase I footprinting. The conformational freedom associated with two netropsins linked by a flexible methylene tether allows ligand binding in both a mono- and bidentate fashion, with bidentate binding requiring a minimum linker length of (CH2)3. For compounds possessing rigid tethers, for example, cis and trans ethylene moieties, the cis geometry excludes bidentate ligation while the trans structure favors it. Bis netropsins possessing aryl linking groups have reduced DNA binding affinities. This is most plausibly due to the aryl groups, which are not coplanar with the netropsin moieties, thus blocking the ligand from penetrating deeply into the minor groove of DNA.

Original languageEnglish (US)
Pages (from-to)162-168
Number of pages7
JournalChemical Research in Toxicology
Volume3
Issue number2
DOIs
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • Toxicology

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