Synthesis and Molecular Modeling of Novel HSV1 Uracil-DNA Glycosylase Inhibitors |
| |
| Authors: | M. Pregnolato D. Ubiali A. Verri F. Focher S. Spadari H. Sun |
| |
| Affiliation: | 1. Dipartimento di Chimica Farmaceutica , Università degli Studi , I-27100, Pavia, Italy;2. Istituto di Genetica Biochimica ed Evoluzionistica, CNR , I-27100, Pavia, Italy;3. Department of Pharmacology and Molecular Toxicology , University of Massachusetts Medical Center , Worcester, MA, 10655 |
| |
| Abstract: | Abstract In a recent paper the first selective inhibitors of HSV1 uracil-DNA glycosylase (UDG) acting in the micromolar range have been reported 1. A 28.5 kDa catalytic fragment of HSV1 UDG has been crystallized in the presence of uracil, and the structure was recently solved2. Starting with the optimized model of binding between 6-(4′-n-octylanilino)uracil (octAU) and UDG some new derivatives have been predicted to be active. In vitro studies with the novel synthetized compounds confirm the plausibility of the model and define the structure features for UDG inhibitors. |
| |
| Keywords: | |
|
|
