Nuclear Magnetic Resonance Solution Structure of an Undecanucleotide Duplex with a Complementary Thymidine Base opposite a 10R Adduct Derived from Trans Addition of a Deoxyadenosine N6-Amino Group to (-)-(7R,8S,9R,10S)-7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene

Eric J. Schurter, Jane M. Sayer, Toshinari Oh-hara, Herman J.C. Yeh, Haruhiko Yagi, Bruce A. Luxon, Donald M. Jerina, David G. Gorenstein

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

The solution structure of a modified undecamer duplex containing (-)-(7R,8S,9R,10S)-7,8- dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene covalently bonded through trans ring opening at C10 of the epoxide by the N6-amino group of deoxyadenosine (dA) was studied. This diol epoxide 1 diastereomer has the benzylic 7-hydroxyl group and the epoxide oxygen cis. The modified nucleotide residue has R chirality at C10 of the hydrocarbon (10R adduct). The undecamer duplex d(C1G2G3T4C5A*6C7G8A9G10G11).d(C12C13T14C15G16T17G18A19C20C21G22) has a complementary T opposite the modified dA (dA*6 is the modified dA). Exchangeable and nonexchangeable proton assignments were made using 2D TOCSY, NOESY, and water/NOESY NMR spectroscopy. The hybrid complete relaxation matrix program MORASS was used to generate NOESY distance constraints for iterative refinement using distance-restrained molecular dynamics calculations. The refined structure showed the hydrocarbon intercalated from the major groove between dA*6-T17 and dC5-dG18 base pairs. The modified dA*6 was in the normal anti configuration and showed Watson-Crick base pairing to T17 opposite. The chemical shifts of the hydrocarbon protons and the unusual shifts of sugar protons were accounted for by the intercalated orientation of the hydrocarbon.

Original languageEnglish (US)
Pages (from-to)9009-9020
Number of pages12
JournalBiochemistry
Volume34
Issue number28
DOIs
StatePublished - Jul 1995

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Nuclear Magnetic Resonance Solution Structure of an Undecanucleotide Duplex with a Complementary Thymidine Base opposite a 10R Adduct Derived from Trans Addition of a Deoxyadenosine N<sup>6</sup>-Amino Group to (-)-(7R,8S,9R,10S)-7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene'. Together they form a unique fingerprint.

  • Cite this