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 Geacintov

Research output: Contribution to journalArticle

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

Fingerprint

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Benzo(a)pyrene
Epoxy Compounds
Oligonucleotides
Guanine
Electrophoretic mobility
Stereochemistry
Hinges
Joints

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Base sequence-dependent bends in site-specific benzo[a]pyrene diol epoxide-modified oligonucleotide duplexes. / Liu, Tongming; Xu, Jing; Tsao, Hong; Li, Bin; Xu, Rong; Yang, Cuijian; Amin, Shantu; Moriya, Masaaki; Geacintov, Nicholas.

In: Chemical Research in Toxicology, Vol. 9, No. 1, 01.1996, p. 255-261.

Research output: Contribution to journalArticle

Liu, Tongming ; Xu, Jing ; Tsao, Hong ; Li, Bin ; Xu, Rong ; Yang, Cuijian ; Amin, Shantu ; Moriya, Masaaki ; Geacintov, Nicholas. / Base sequence-dependent bends in site-specific benzo[a]pyrene diol epoxide-modified oligonucleotide duplexes. In: Chemical Research in Toxicology. 1996 ; Vol. 9, No. 1. pp. 255-261.
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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.",
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AU - Liu, Tongming

AU - Xu, Jing

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AU - Li, Bin

AU - Xu, Rong

AU - Yang, Cuijian

AU - Amin, Shantu

AU - Moriya, Masaaki

AU - Geacintov, Nicholas

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AB - 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.

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