Solution structure of the aminofluorene [AF]-intercalated conformer of the syn-[AF]-C(8)-dG adduct opposite dC in a DNA duplex Journal Article

  

Authors:	Mao, B.; Hingerty, B. E.; Broyde, S.; Patel, D. J.
Article Title:	Solution structure of the aminofluorene [AF]-intercalated conformer of the syn-[AF]-C(8)-dG adduct opposite dC in a DNA duplex
Abstract:	We report below on a conformational equilibrium between AF-intercalated and AF-external states in slow exchange for the [AF]dG lesion positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context. The slow exchange between states is attributed to interconversion between syn glycosidic torsion angle in the AF-intercalated and anti torsion angle in AF-external conformers of the [AF]dG opposite dC containing duplex. The present paper describes an NMR-molecular mechanics study that defines the solution structure of the AF-intercalated conformer for the case of [AF]dG adduct positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context. The structure is of the base displacement-intercalation type where the aminofluorene ring is intercalated into the helix between intact Watson- Crick dG·dC base pairs, which results in a displacement of the modified guanine ring into the major groove where it stacks with the major groove edge of its 5'-flanking cytosine in the adduct duplex. The conformational equilibrium between AF-intercalated conformer (~70%) with a syn alignment and AF-external conformer (~30%) with an anti alignment for the [AF]dG adduct positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context can be contrasted with our earlier demonstration that the population is 100% for the AP-intercalated conformer with a syn alignment at the N- (deoxyguanosin-8-yl)-2-aminopyrene ([AP]dG) adduct site positioned opposite dC in the same sequence context [Mao, B., Vyas, R. R., Hingerty, B. E., Broyde, S., Basu, A. K., and Patel, D. J. (1996) Biochemistry, 35, 12659- 12670]. This shift in population may reflect the much larger size of the pyrenyl ring of the [AP]dG adduct compared to the fluorenyl ring of the [AF]dG adduct which in turn might provide for a greater overlap of the aromatic amine with the flanking base pairs in the intercalated conformer of the former adduct in DNA.
Keywords:	molecular dynamics; double stranded dna; magnetic resonance spectroscopy; deoxyguanosine; base pairing; dna adduct; dna structure; dna adducts; models, molecular; protons; solutions; molecular structure; nucleic acid conformation; structure analysis; deoxycytidine; mathematical computing; dna determination; nuclear magnetic resonance; fluorenes; carbon; phosphorus; carcinogens; nucleic acid heteroduplexes; nuclear overhauser effect; intercalating agents; priority journal; article; 2 fluorenylamine
Journal Title:	Biochemistry
Volume:	37
Issue:	1
ISSN:	0006-2960
Publisher:	American Chemical Society
Date Published:	1998-01-06
Start Page:	81
End Page:	94
Language:	English
DOI:	10.1021/bi972257o
PUBMED:	9425028
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0032488634&doi=10.1021%2fbi972257o&partnerID=40&md5=9ae9c2d8b6212b9f6183bcd8b40227ec
Notes:	Article -- Export Date: 12 December 2016 -- Source: Scopus

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