Smoothed Potential MD Simulations for Dissociation Kinetics of Etoposide To Unravel Isoform Specificity in Targeting Human Topoisomerase II.

ABSTRACT: Human type II topoisomerases (TopoII) are essential for controlling DNA topology within the cell. For this reason, there are a number of TopoII-targeted anticancer drugs that act by inducing DNA cleavage mediated by both TopoII isoforms (TopoIIα and TopoIIβ) in cells. However, recent studies suggest that specific poisoning of TopoIIα may be a safer strategy for treating cancer. This is because poisoning of TopoIIβ appears to be linked to the generation of secondary leukemia in patients. We recently reported that enzyme-mediated DNA cleavage complexes (in which TopoII is covalently linked to the cleaved DNA during catalysis) formed in the presence of the anticancer drug etoposide persisted approximately 3-fold longer with TopoIIα than TopoIIβ. Notably, enhanced drug-target residence time ma

SUBMITTER: Kuriappan JA 

PROVIDER: S-EPMC6800198 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature