| Autor: |
Joseph C. Calabrese, Ayelet Nudelman, Alan R. Rendina, Zdislaw Wawrzak, Dana Marcovici-Mizrahi, George H. Lorimer, Wendy Sue Taylor, Gunter Schneider, Abraham Nudelman, Bruce A. Lockett, W. Huang, Guang Yang, Kevin T. Kranis, Dennis R. Rayner, Barry Arthur Wexler, Ylva Lindqvist, Hongji Chi, Eileen Marsilii, Katharine J. Gibson, Jia Jia |
| Rok vydání: |
1999 |
| Předmět: |
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| Zdroj: |
Pesticide Science. 55:236-247 |
| ISSN: |
0031-613X |
| DOI: |
10.1002/(sici)1096-9063(199903)55:3<236::aid-ps888>3.0.co;2-0 |
| Popis: |
Dethiobiotin synthetase (DTBS; E.C. 6.6.6.6), the penultimate enzyme in the biosynthesis of the essential vitamin biotin, is a new potential target for novel herbicides. Inhibitors were designed based on mechanistic and structural information. The in-vitro activities of these potential inhibitors versus the bacterial enzyme are reported here. Mimics of 7,8-diaminopelargonic acid (DAPA) or the DAPA carbamate reaction intermediate were substrates or partial substrates for the enzyme. Synergistic binding with ATP was noted with compounds which contained an amino functionality. NMR studies and X-ray structures confirmed that the inhibitors could be phosphorylated by the enzyme. Several series of potential inhibitors were designed to take advantage of this partial substrate activity by generating potentially more tightly bound phosphorylated inhibitors in situ. Structure-activity relationships for these series based on both substrate and inhibitory activity are described herein. An X-ray structure for one of these inhibitors is also discussed. Although considerable potential for inhibitors of this type was demonstrated, none of the compounds reported showed sufficient herbicidal activity to be a commercial proposition. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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