ISSN:
1432-2234
Keywords:
Key words: DNA sequence
;
DNA structure
;
Molecular modelling
;
Radioprotection
;
WR thiols
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract. Sequence-dependent variations of DNA structure modulate radiation-induced strand breakage. Thiols reduce breakage by scavenging damaging radiolytic OH . and repairing sugar radicals. As shown by sequencing gel electrophoresis, WR-1065 radioprotection is modulated by sequence, whereas that of WR-151326, a larger thiol, is more evenly distributed. Molecular modelling was performed on complexes of a 53 bp oligonucleotide (belonging to a natural restriction fragment) with one molecule of WR-1065 or WR-151326. Energy minimised structures exhibit a broadening of the minor groove of an AAATT motif upon WR-1065 binding, and a narrowing of the groove upon WR-151326 binding. Consequently, the accessibility to OH˙ of H4′ (whose abstraction leads to strand breakage) increases near WR-1065, whereas it decreases near WR-151326. This modifies locally the otherwise homogeneous radioprotection. The effect of WR-151326 strengthens the protection at all tested binding sites, whereas that of WR-1065 diminishes it in some regions, in good agreement with the observed radioprotection distribution.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002140050416
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