MEDI 250 |
| Methionine aminopeptidase (MetAP) catalyze the removal of the N-terminal methionine from newly synthesized proteins in all types of cells. Inhibitors of MetAPs are of considerable interest as potential antibacterial, antifungal and anticancer agents. All MetAPs require a divalent metal ion such as Mn(II), Fe(II), Co(II) for activity, but it is not certain which of these ions is most important in vivo. Relatively few nonpeptidic MetAP inhibitors are known, and they either show low selectivity among various metalloforms in vitro or have not been tested on metalloforms other than the Co(II)-form. New metalloform-selective MetAP inhibitors are valuable for defining which metals are physiologically important for MetAP activation and could serve as leads for development of new therapeutic agents. We have screened a library of small drug-like molecules against E. coli MetAP and discovered groups of unique inhibitors of this enzyme that are not only potent but highly selective for different metalloforms. |
|
High Throughput Screening and Drug Discovery
9:00 AM-12:20 PM, Wednesday, March 28, 2007 McCormick Place Lakeside -- Room E353 C, Level 3, Oral
Division of Medicinal Chemistry |