Human topoisomerase I inhibition: docking camptothecin and derivatives into a structure-based active site model.

@article{Laco2002HumanTI,
  title={Human topoisomerase I inhibition: docking camptothecin and derivatives into a structure-based active site model.},
  author={Gary S. Laco and Jack R. Collins and Brian T. Luke and Heiko Kroth and Jane M. Sayer and Donald M. Jerina and Yves Pommier},
  journal={Biochemistry},
  year={2002},
  volume={41 5},
  pages={1428-35}
}
Human topoisomerase I (top1) is an important target for anti-cancer drugs, which include camptothecin (CPT) and its derivatives. To elucidate top1 inhibition in vitro, we made a series of duplex DNA substrates containing a deoxyadenosine stereospecifically modified by a covalent adduct of benzo[a]pyrene (BaP) diol epoxide [Pommier, Y., et al. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 10739-10744]. The known orientation of the hydrocarbon adduct in the DNA duplex relative to the top1 cleavage… CONTINUE READING