Base sequence-dependent bends in site-specific benzo[a]pyrene diol epoxide-modified oligonucleotide duplexes

Tongming Liu, Jing Xu, Hong Tsao, Bin Li, Rong Xu, Cuijian Yang, Shantu Amin, Masaaki Moriya, Nicholas E. Geacintov

Research output: Contribution to journalArticlepeer-review

Abstract

The site specifically modified oligonucleotides 5'-d(TCCTCCTG1G2CCTCTC) (I) and 5'-d(CTATG1G2G3TATC) (II) were synthesized with single modified guanine residues at positions G1, G2, or G3, derived from the covalent binding reaction of 7R,8S-dihydroxy-9S, 10R-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene ((+)-anti-BPDE) with the exocyclic amino groups of the guanine residues. In denaturing 20% polyacrylamide gels, the electrophoretic mobilities of the (+)-anti-BPDE-modified oligonucleotides I and II are slower than the mobilities of the respective unmodified oligonucleotides and independent of the positions of the BPDE-modified guanines. However, in the double-stranded forms in native 8% polyacrylamide gels, the electrophoretic mobilities of the duplexes with lesions at G2 or G3 are remarkably slower (reductions in mobilities up to ~40%) than to duplexes with lesions at G1 and are attributed to physical bends or flexible hinge joints at the sites of the BPDE lesions. These sequence-dependent mobility effects occur whenever the BPDE-modified guanine residues with (+)- trans-stereochemistry are flanked by unmodified G's on the 5'-side. These retarded electrophoretic mobilities are attributed to bending induced by steric hindrance effects involving the bulky 5'-flanking guanines and the pyrenyl residues that are known to point into the 5'-direction relative to the modified G [Cosman, M., et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 19141918]. These anomalous electrophoretic mobility effects are not observed in the case of (-)-anti-BPDE-modified sequences I with trans-(-)-anti-BPDE- N2-dG adduct stereochemistry.

Original languageEnglish (US)
Pages (from-to)255-261
Number of pages7
JournalChemical research in toxicology
Volume9
Issue number1
DOIs
StatePublished - Jan 1996

ASJC Scopus subject areas

  • Toxicology

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