Conformational interconversion of the trans-4-hydroxynonenal-derived (6S,8R,11S) l,N 2-deoxyguanosine adduct when mismatched with deoxyadenosine in DNA

Hai Huang, Hao Wang, Robert (Stephen) Lloyd, Carmelo J. Rizzo, Michael P. Stone

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The (6S,8R,11S) l,N 2-HNE-dGuo adduct of trans-4-hydroxynonenal (HNE) was incorporated into the duplex 5′-d(GCTAGCXAGTCC)-3′- 5′-d(GGACTAGCTAGC)-3′ [X = 6S,8R,11S) HNE-dG], in which the lesion was mismatched opposite dAdo. The (6S,8/?,115) adduct maintained the ring-closed 1,N 2- HNE-dG structure. This was in contrast to when this adduct was correctly paired with dCyd, conditions under which it underwent ring opening and rearrangement to diastereomeric minor groove cyclic hemiacetals [Huang, H., Wang, H., Qi, N., Lloyd, R. S., Harris, T. M., Rizzo, C. J., and Stone, M. P. (2008) J. Am. Chem. Soc. 130,10898-10906]. The (6S,8R,11S) adduct exhibited a synlanti conformational equilibrium about the glycosyl bond. The syn conformation was predominant in acidic solution. Structural analysis of the syn conformation revealed that X 7 formed a distorted base pair with the complementary protonated A 18. The HNE moiety was located in the major groove. Structural perturbations were observed at the neighbor C 6·G 19 and A 8·T 17 base pairs. At basic pH, the anti conformation of X 7 was the major species. The 1,N 2-HNE-dG intercalated and displaced the complementary A 18 in the 5′-direction, resulting in a bulge at the X 7·A 18 base pair. The HNE aliphatic chain was oriented toward the minor groove. The Watson - Crick hydrogen bonding of the neighboring A 8·T 17 base pair was also disrupted.

Original languageEnglish (US)
Pages (from-to)187-200
Number of pages14
JournalChemical Research in Toxicology
Volume22
Issue number1
DOIs
StatePublished - Jan 2009

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Deoxyguanosine
Base Pairing
Conformations
DNA
Structural analysis
Hydrogen bonds
Hydrogen Bonding
2'-deoxyadenosine
4-hydroxy-2-nonenal
8-nitro-2'-deoxyguanosine

ASJC Scopus subject areas

  • Toxicology

Cite this

Conformational interconversion of the trans-4-hydroxynonenal-derived (6S,8R,11S) l,N 2-deoxyguanosine adduct when mismatched with deoxyadenosine in DNA. / Huang, Hai; Wang, Hao; Lloyd, Robert (Stephen); Rizzo, Carmelo J.; Stone, Michael P.

In: Chemical Research in Toxicology, Vol. 22, No. 1, 01.2009, p. 187-200.

Research output: Contribution to journalArticle

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title = "Conformational interconversion of the trans-4-hydroxynonenal-derived (6S,8R,11S) l,N 2-deoxyguanosine adduct when mismatched with deoxyadenosine in DNA",
abstract = "The (6S,8R,11S) l,N 2-HNE-dGuo adduct of trans-4-hydroxynonenal (HNE) was incorporated into the duplex 5′-d(GCTAGCXAGTCC)-3′- 5′-d(GGACTAGCTAGC)-3′ [X = 6S,8R,11S) HNE-dG], in which the lesion was mismatched opposite dAdo. The (6S,8/?,115) adduct maintained the ring-closed 1,N 2- HNE-dG structure. This was in contrast to when this adduct was correctly paired with dCyd, conditions under which it underwent ring opening and rearrangement to diastereomeric minor groove cyclic hemiacetals [Huang, H., Wang, H., Qi, N., Lloyd, R. S., Harris, T. M., Rizzo, C. J., and Stone, M. P. (2008) J. Am. Chem. Soc. 130,10898-10906]. The (6S,8R,11S) adduct exhibited a synlanti conformational equilibrium about the glycosyl bond. The syn conformation was predominant in acidic solution. Structural analysis of the syn conformation revealed that X 7 formed a distorted base pair with the complementary protonated A 18. The HNE moiety was located in the major groove. Structural perturbations were observed at the neighbor C 6·G 19 and A 8·T 17 base pairs. At basic pH, the anti conformation of X 7 was the major species. The 1,N 2-HNE-dG intercalated and displaced the complementary A 18 in the 5′-direction, resulting in a bulge at the X 7·A 18 base pair. The HNE aliphatic chain was oriented toward the minor groove. The Watson - Crick hydrogen bonding of the neighboring A 8·T 17 base pair was also disrupted.",
author = "Hai Huang and Hao Wang and Lloyd, {Robert (Stephen)} and Rizzo, {Carmelo J.} and Stone, {Michael P.}",
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T1 - Conformational interconversion of the trans-4-hydroxynonenal-derived (6S,8R,11S) l,N 2-deoxyguanosine adduct when mismatched with deoxyadenosine in DNA

AU - Huang, Hai

AU - Wang, Hao

AU - Lloyd, Robert (Stephen)

AU - Rizzo, Carmelo J.

AU - Stone, Michael P.

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N2 - The (6S,8R,11S) l,N 2-HNE-dGuo adduct of trans-4-hydroxynonenal (HNE) was incorporated into the duplex 5′-d(GCTAGCXAGTCC)-3′- 5′-d(GGACTAGCTAGC)-3′ [X = 6S,8R,11S) HNE-dG], in which the lesion was mismatched opposite dAdo. The (6S,8/?,115) adduct maintained the ring-closed 1,N 2- HNE-dG structure. This was in contrast to when this adduct was correctly paired with dCyd, conditions under which it underwent ring opening and rearrangement to diastereomeric minor groove cyclic hemiacetals [Huang, H., Wang, H., Qi, N., Lloyd, R. S., Harris, T. M., Rizzo, C. J., and Stone, M. P. (2008) J. Am. Chem. Soc. 130,10898-10906]. The (6S,8R,11S) adduct exhibited a synlanti conformational equilibrium about the glycosyl bond. The syn conformation was predominant in acidic solution. Structural analysis of the syn conformation revealed that X 7 formed a distorted base pair with the complementary protonated A 18. The HNE moiety was located in the major groove. Structural perturbations were observed at the neighbor C 6·G 19 and A 8·T 17 base pairs. At basic pH, the anti conformation of X 7 was the major species. The 1,N 2-HNE-dG intercalated and displaced the complementary A 18 in the 5′-direction, resulting in a bulge at the X 7·A 18 base pair. The HNE aliphatic chain was oriented toward the minor groove. The Watson - Crick hydrogen bonding of the neighboring A 8·T 17 base pair was also disrupted.

AB - The (6S,8R,11S) l,N 2-HNE-dGuo adduct of trans-4-hydroxynonenal (HNE) was incorporated into the duplex 5′-d(GCTAGCXAGTCC)-3′- 5′-d(GGACTAGCTAGC)-3′ [X = 6S,8R,11S) HNE-dG], in which the lesion was mismatched opposite dAdo. The (6S,8/?,115) adduct maintained the ring-closed 1,N 2- HNE-dG structure. This was in contrast to when this adduct was correctly paired with dCyd, conditions under which it underwent ring opening and rearrangement to diastereomeric minor groove cyclic hemiacetals [Huang, H., Wang, H., Qi, N., Lloyd, R. S., Harris, T. M., Rizzo, C. J., and Stone, M. P. (2008) J. Am. Chem. Soc. 130,10898-10906]. The (6S,8R,11S) adduct exhibited a synlanti conformational equilibrium about the glycosyl bond. The syn conformation was predominant in acidic solution. Structural analysis of the syn conformation revealed that X 7 formed a distorted base pair with the complementary protonated A 18. The HNE moiety was located in the major groove. Structural perturbations were observed at the neighbor C 6·G 19 and A 8·T 17 base pairs. At basic pH, the anti conformation of X 7 was the major species. The 1,N 2-HNE-dG intercalated and displaced the complementary A 18 in the 5′-direction, resulting in a bulge at the X 7·A 18 base pair. The HNE aliphatic chain was oriented toward the minor groove. The Watson - Crick hydrogen bonding of the neighboring A 8·T 17 base pair was also disrupted.

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