Journal article
Synthesis and evaluation of inhibitors for Escherichia coli carbamyl phosphate synthetase
Bioorganic chemistry, Vol.17(4), pp.422-433
1989
DOI: 10.1016/0045-2068(89)90043-6
Abstract
The design, synthesis, and evaluation of potential multisubstrate analog inhibitors for
Escherichia coli carbamyl phosphate synthetase (CPS) are described. The inhibitors, which combine structural features of glutamine plus ammonia or of glutamine plus a mimic of the electrophilic ammonia acceptor, were designed to probe the spatial relationship between the substrate binding sites on the two subunits of the enzyme. Of the inhibitors described, 2-amino-3-[(
N-phosphorylglycyl)amino]propanoate,
2a, with a
K
i
value of 60 μ
m, represents the most potent reversible inhibitor yet reported for
E. coli CPS. The synthetic route to the inhibitors utilized a convenient protection strategy whose refinement was described previously for manipulating ω-amino- or ω-carboxyl-substituted α-amino acids (J. M. Scholtz and P. A. Bartlett, 1988,
Synthesis, 542).
Details
- Title: Subtitle
- Synthesis and evaluation of inhibitors for Escherichia coli carbamyl phosphate synthetase
- Creators
- John M. Scholtz - University of California, BerkeleyPaul A. Bartlett - University of California, Berkeley
- Resource Type
- Journal article
- Publication Details
- Bioorganic chemistry, Vol.17(4), pp.422-433
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0045-2068(89)90043-6
- ISSN
- 0045-2068
- eISSN
- 1090-2120
- Language
- English
- Date published
- 1989
- Academic Unit
- Research Administration; Pharmaceutical Sciences and Experimental Therapeutics; Biochemistry and Molecular Biology; Chemistry
- Record Identifier
- 9984293073702771
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