Intercalation of aflatoxin B sub 1 in two oligodeoxynucleotide adducts: Comparative sup 1 H NMR analysis of d(ATC sup AFB GAT)ter dot d(ATCGAT) and d(AT sup ATB GCAT) sub 2

Journal Article · Thu Nov 01 00:00:00 EST 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00498a002· OSTI ID:5671601

Gopalakrishnan, S; Harris, T M; Stone, M P ^[1]

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1. Vanderbilt Univ., Nashville, TN (USA)

8,9-Dihydro-8-(N7-guanyl-(d(ATCGAT)))-9-hydroxyaflatoxin B{sub 1}{center dot}d(ATCGAT) and 8,9-dihydro-8-(N7-guanyl-(d(ATGCAT)))-9-hydroxyafltoxin B{sub 1}{center dot}8,9-dihydro-8-(N7-guanyl-(d(ATGCAT)))-9-hydroxyaflatoxin B{sub 1} were prepared by direct addition of aflatoxin B{sub 1} 8,9-expoxide to d(ATCGAT){sub 2} and d(ATGCAT){sub 2}, respectively. {sup 1}H NOE experiments, nonselective {sup 1}H T{sub 1} relaxation measurements, and {sup 1}H chemical shift perturbations demonstrate that in both modified oligodeoxynucleotides the aflatoxin moiety is intercalated above the 5{prime}-face of the modified guanine. The oligodeoxynucleotides remain right-handed, and perturbation of the B-DNA structure is localized adjacent to the adducted guanine. Aflatoxin-oligodeoxynucleotide {sup 1}H NOEs are observed between aflatoxin and the 5{prime}-neighbor base pair and include both the major groove and the minor groove. The protons at C8 and C9 of the aflatoxin terminal furan ring exhibit slower spin-lattice relaxation as compared to other oligodeoxynucleotide protons, which supports the conclusion that they face into the major groove. Increased shielding is observed for aflatoxin protons. The difference in reaction stoichiometry is consistent with an intercalated transition-state complex between aflatoxin B{sub 1} 8,9-epoxide and B-DNA. Intercalation provides excellent positioning for nucleophilic attack by guanine N7 on aflatoxin B{sub 1} 8,9-epoxide, which probably accounts for the observed efficiency of adduct formation despite the relatively low DNA binding affinity observed for aflatoxin B{sub 1}.

• OSTI ID: 5671601
• Journal Information: Biochemistry; (USA), Vol. 29:46; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AFLATOXINS
GENETIC EFFECTS
DNA ADDUCTS
NUCLEAR MAGNETIC RESONANCE
ASPERGILLUS
CHEMICAL SHIFT
EPOXIDES
FURANS
GUANINE
OLIGONUCLEOTIDES
ADDUCTS
AMINES
ANTIGENS
AROMATICS
AZAARENES
BIOLOGICAL EFFECTS
EUMYCOTA
FUNGI
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
MAGNETIC RESONANCE
MATERIALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PLANTS
PURINES
RESONANCE
TOXIC MATERIALS
TOXINS
550201* - Biochemistry- Tracer Techniques