All-Atom Molecular Dynamics Reveals Mechanism of Zinc Complexation with Therapeutic F10.

ABSTRACT: Advancing the use of therapeutic nucleic acids requires understanding the chemical and structural properties that allow these polymers to promote the death of malignant cells. Here we explore Zn²⁺ complexation by the fluoropyrimidine polymer F10, which has strong activities in multiple preclinical models of cancer. Delivery of fluoropyrimidine FdUMP in the 10-residue polymer F10 rather than the nucleobase (5-fluorouracil) allows consideration of metal ion binding effects on drug delivery. The differences in metal ion interactions with fluoropyrimidine compared to normal DNA results in conformation changes that affect protein binding, cell uptake, and codelivery of metals such as zinc, and the cytoxicity thereof. Microsecond-time-scale, all-atom simulations of F10 predict that zi

SUBMITTER: Melvin RL 

PROVIDER: S-EPMC5956911 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature