Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1

0457638 - BFÚ 2016 RIV GB eng J - Článek v odborném periodiku
Malina, Jaroslav - Scott, P. - Brabec, Viktor
Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1.
Nucleic Acids Research. Roč. 43, č. 11 (2015), s. 5297-5306. ISSN 0305-1048. E-ISSN 1362-4962
Grant CEP: GA ČR(CZ) GAP205/11/0856
Institucionální podpora: RVO:68081707
Klíčová slova: BASE EXCISION-REPAIR * CYTOSINE OPPOSITE * BINDING
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 9.202, rok: 2015

Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo-helical 'flexicate' complexes, bimetallic triple-stranded ferro-helicates [Fe-2(NN-NN)(3)](4+) incorporating the common NN-NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Lambda-enantiomer binds to all tested AP sites with higher affinity than the Delta-enantiomer.
Trvalý link: http://hdl.handle.net/11104/0258034