Effects of neutralization pattern and stereochemistry on DNA bending by methylphosphonate substitutions

J. K. Strauss-Soukup, M. M. Vaghefi, R. I. Hogrefe, L. J. Maher

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Asymmetric phosphate neutralization has been hypothesized to play a role in DNA bending by proteins. Neutralization is thought to involve salt bridges between the negatively charged phosphate backbone of duplex DNA and the cationic amino acids of an approaching protein. According to this model, the resulting unbalanced charge distribution along the duplex DNA induces the double helix to collapse toward the neutralized surface. Previous work has confirmed that DNA bending is induced by the asymmetric incorporation of racemic methylphosphonate linkages creating a neutral region on one face of duplex DNA. Neutralization was accomplished by substitution of three consecutive phosphodiesters on each strand, arranged across one minor groove of the DNA (a total of six neutralized phosphates). We now measure DNA bending induced by a more diffuse patch of neutralization (alternating neutralized and anionic phosphates) and explore the effect of methylphosphonate stereochemistry. DNA duplexes with patches of alternating methylphosphonate and phosphodiester linkages are less bent than DNAs wherein consecutive phosphates ale neutralized. Furthermore, duplexes neutralized by incorporation of pure (Rp)-methylphosphonate isomers are bent ~30% less than duplexes neutralized by racemic methylphosphonates.

Original languageEnglish (US)
Pages (from-to)8692-8698
Number of pages7
JournalBiochemistry
Volume36
Issue number29
DOIs
StatePublished - Jul 22 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry

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