Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1375786 | Bioorganic & Medicinal Chemistry Letters | 2008 | 8 Pages |
Abstract
Molecular dynamics simulations and free energy calculations are presented, exploring previously described experimentally studied interactions of a series of 2â²-fluoro-substituted dUMP/FdUMP analogues with thymidylate synthase (TS). The results show the inhibitory behaviors of 2â²-F-ara-UMP, 2â²,2â³-diF-dUMP and 2â²,5-diF-ara-UMP to be dependent upon the binding positions and orientations adopted by the molecules of these compounds in the active site of TS. The binding mode of 2â²,5-diF-ara-UMP suggests a novel role of the active site residue Trp 80, stabilizing through hydrophobic stacking the binding position of the pyrimidine ring in 2â²,5-diF-ara-UMP.
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Adam JarmuÅa, Anna DowierciaÅ, Wojciech Rode,