Analysis of human topoisomerase I inhibition and interaction with the cleavage site +1 deoxyguanosine, via in vitro experiments and molecular modeling studies.

@article{Laco2004AnalysisOH,
  title={Analysis of human topoisomerase I inhibition and interaction with the cleavage site +1 deoxyguanosine, via in vitro experiments and molecular modeling studies.},
  author={Gary S. Laco and Wu Du and Glenda Kohlhagen and Jane M. Sayer and Donald M. Jerina and Thomas G. Burke and Dennis P Curran and Yves Pommier},
  journal={Bioorganic & medicinal chemistry},
  year={2004},
  volume={12 19},
  pages={5225-35}
}
Human topoisomerase I (Top1) plays a pivotal role in cell replication and transcription, and therefore is an important anti-cancer target. Homocamptothecin is a lead compound for inhibiting Top1, and is composed of five conjugated planar rings (A-E). The homocamptothecin E-ring beta-hydroxylactone opens slowly to a carboxylate at pH>7.0. We analyzed, which form of homocamptothecin was biochemically relevant in the following ways: (1) the homocamptothecin carboxylate was tested for activity in… CONTINUE READING