Total Synthesis, Mass Spectrometric Sequencing, and Stabilities of Oligonucleotide Duplexes with Single trans-anti-BPDE-N6-dA Lesions in the N-ras codon 61 and Other Sequence Contexts

Jacek Krzeminski; Jinsong Ni; Ping Zhuang; Natalia Luneva; Shantu Amin; Nicholas E. Geacintov

doi:10.1080/10406639908020596

Total Synthesis, Mass Spectrometric Sequencing, and Stabilities of Oligonucleotide Duplexes with Single trans-anti-BPDE-N⁶-dA Lesions in the N-ras codon 61 and Other Sequence Contexts

Jacek Krzeminski, Jinsong Ni, Ping Zhuang, Natalia Luneva, Shantu Amin, Nicholas E. Geacintov

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Three different oligonucleotides (one of them comprising a portion of the N-ras protooncogene) with single bay region anti-BPDE-modified adenine residues (anti-BPDE = 7r,8t-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) were prepared by total synthesis methods, characterized, and sequenced by electrospray tandem mass spectrometry techniques. While all of the BPDE-modified duplexes are destabilized relative to the unmodified double-stranded oligonucleotides, the thermodynamic stabilities of duplexes containing 105 (+)-trans-lesions are consistently lower than those of duplexes containing the stereoisomeric 10R (-)-trans adducts. In contrast, similar duplexes, but with fjord region BcPhDE-N⁶-dA adducts are not thermodynamically destabilized by these bulky lesions (anti-BcPhDE: 4r,3t-dihydroxy-t1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene).

Original language	English (US)
Pages (from-to)	1-10
Number of pages	10
Journal	Polycyclic Aromatic Compounds
Volume	17
Issue number	1-4
DOIs	https://doi.org/10.1080/10406639908020596
State	Published - 1999

Keywords

Benzo[a]pyrene diol epoxide
Benzo[c]phenanthrene diol epoxide
DNA adducts
Deoxyadenosine lesions
Stereochemistry
Thermodynamic stability

ASJC Scopus subject areas

Organic Chemistry
Polymers and Plastics
Materials Chemistry

Access to Document

10.1080/10406639908020596

Cite this

Total Synthesis, Mass Spectrometric Sequencing, and Stabilities of Oligonucleotide Duplexes with Single trans-anti-BPDE-N⁶-dA Lesions in the N-ras codon 61 and Other Sequence Contexts. / Krzeminski, Jacek; Ni, Jinsong; Zhuang, Ping et al.
In: Polycyclic Aromatic Compounds, Vol. 17, No. 1-4, 1999, p. 1-10.

Research output: Contribution to journal › Article › peer-review

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title = "Total Synthesis, Mass Spectrometric Sequencing, and Stabilities of Oligonucleotide Duplexes with Single trans-anti-BPDE-N6-dA Lesions in the N-ras codon 61 and Other Sequence Contexts",

abstract = "Three different oligonucleotides (one of them comprising a portion of the N-ras protooncogene) with single bay region anti-BPDE-modified adenine residues (anti-BPDE = 7r,8t-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) were prepared by total synthesis methods, characterized, and sequenced by electrospray tandem mass spectrometry techniques. While all of the BPDE-modified duplexes are destabilized relative to the unmodified double-stranded oligonucleotides, the thermodynamic stabilities of duplexes containing 105 (+)-trans-lesions are consistently lower than those of duplexes containing the stereoisomeric 10R (-)-trans adducts. In contrast, similar duplexes, but with fjord region BcPhDE-N6-dA adducts are not thermodynamically destabilized by these bulky lesions (anti-BcPhDE: 4r,3t-dihydroxy-t1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene).",

keywords = "Benzo[a]pyrene diol epoxide, Benzo[c]phenanthrene diol epoxide, DNA adducts, Deoxyadenosine lesions, Stereochemistry, Thermodynamic stability",

author = "Jacek Krzeminski and Jinsong Ni and Ping Zhuang and Natalia Luneva and Shantu Amin and Geacintov, {Nicholas E.}",

note = "Funding Information: This work was supported by NIH Grants CA 20851 and CA 17613.",

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T1 - Total Synthesis, Mass Spectrometric Sequencing, and Stabilities of Oligonucleotide Duplexes with Single trans-anti-BPDE-N6-dA Lesions in the N-ras codon 61 and Other Sequence Contexts

AU - Krzeminski, Jacek

AU - Ni, Jinsong

AU - Zhuang, Ping

AU - Luneva, Natalia

AU - Amin, Shantu

AU - Geacintov, Nicholas E.

N1 - Funding Information: This work was supported by NIH Grants CA 20851 and CA 17613.

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N2 - Three different oligonucleotides (one of them comprising a portion of the N-ras protooncogene) with single bay region anti-BPDE-modified adenine residues (anti-BPDE = 7r,8t-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) were prepared by total synthesis methods, characterized, and sequenced by electrospray tandem mass spectrometry techniques. While all of the BPDE-modified duplexes are destabilized relative to the unmodified double-stranded oligonucleotides, the thermodynamic stabilities of duplexes containing 105 (+)-trans-lesions are consistently lower than those of duplexes containing the stereoisomeric 10R (-)-trans adducts. In contrast, similar duplexes, but with fjord region BcPhDE-N6-dA adducts are not thermodynamically destabilized by these bulky lesions (anti-BcPhDE: 4r,3t-dihydroxy-t1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene).

AB - Three different oligonucleotides (one of them comprising a portion of the N-ras protooncogene) with single bay region anti-BPDE-modified adenine residues (anti-BPDE = 7r,8t-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) were prepared by total synthesis methods, characterized, and sequenced by electrospray tandem mass spectrometry techniques. While all of the BPDE-modified duplexes are destabilized relative to the unmodified double-stranded oligonucleotides, the thermodynamic stabilities of duplexes containing 105 (+)-trans-lesions are consistently lower than those of duplexes containing the stereoisomeric 10R (-)-trans adducts. In contrast, similar duplexes, but with fjord region BcPhDE-N6-dA adducts are not thermodynamically destabilized by these bulky lesions (anti-BcPhDE: 4r,3t-dihydroxy-t1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene).

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KW - Thermodynamic stability

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