Computational analysis of the effects of site-specific phosphate alkylation in the DNA oligomer {d-[GGAATTCC]}2
✍ Scribed by Michelle S. Broido; Mihaly Mezei
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 1990
- Tongue
- English
- Weight
- 911 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0006-3525
No coin nor oath required. For personal study only.
✦ Synopsis
D c p a r t i i w r i t of Chemistrv dnd Center for the Study of Gem1 Structurt' and Function Huntrv Coll~qc. ~i i d ihc C j r d u a t r S( hool o i CUNY 695 P x k Avrnuc NCW York NWL York 10021 SYNOPSIS Alkylation of the sugar-phosphate backbone of I)NA can result upon exposure t o several potent carcinogens, inducing DNA misfunction. In order t o assess the structural and energetic changes in DNA helices induced by such alkylation, we have performed AMHER-based analyses on phosphotriester containing analogues of { d-[GGAA'N'CC] )?.
Fourteen analogues of the nonalkylated oligomer were examined, each bearing a single alkylation of known stereochemistry. Hcsults indicate that although there is minimal effect on the aromatic bases, the presenct' of a phosphotriester disturbs the sugar-phosphate backbone in complex ways. For most analogues, total minimum energies are lower for the S,,-alkylations than for the R,,-alhylations which point directly into the ma,jor groove of the helix; however, different energetic contributions follow different, or no. trends in dependence on alkylation site and/or stereochemistry. Where data is available. experimental nmr results agree with the calculations reported here. ' 19%) .John Wiley & Sons, Inc.