Abstract:
:To evaluate the structural influence of the DNA phosphate backbone on the activity of Escherichia coli DNA topoisomerase I, modified forms of oligonucleotide dA(7) were synthesized with a chiral phosphorothioate replacing the non-bridging oxygens at each position along the backbone. A deoxy-iodo-uracil replaced the 5'-base to crosslink the oligonucleotides by ultraviolet (UV) and assess binding affinity. At the scissile phosphate there was little effect on the cleavage rate. At the +1 phosphate, the rectus phosphorus (Rp)-thio-substitution reduced the rate of cleavage by a factor of 10. At the +3 and -2 positions from the scissile bond, the Rp-isomer was cleaved at a faster rate than the sinister phosphorus (Sp)-isomer. The results demonstrate the importance of backbone contacts between DNA substrate and E. coli topoisomerase I.
journal_name
Int J Biol Macromoljournal_title
International journal of biological macromoleculesauthors
Roche CJ,Tse-Dinh YCdoi
10.1016/s0141-8130(01)00165-9keywords:
subject
Has Abstractpub_date
2001-10-22 00:00:00pages
175-80issue
3eissn
0141-8130issn
1879-0003pii
S0141-8130(01)00165-9journal_volume
29pub_type
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