National Research Center, Giza, Egypt.
Synthesis of inhibitors of the meso-diaminopimelate-adding enzyme from Escherichia coli
Article first published online: 12 JAN 2009
International Journal of Peptide and Protein Research
Volume 32, Issue 3, pages 208–222, September 1988
How to Cite
ABO-GHALIA, M., FLEGEL, M., BLANOT, D. and VAN HEIJENOORT, J. (1988), Synthesis of inhibitors of the meso-diaminopimelate-adding enzyme from Escherichia coli. International Journal of Peptide and Protein Research, 32: 208–222. doi: 10.1111/j.1399-3011.1988.tb00936.x
- Issue published online: 12 JAN 2009
- Article first published online: 12 JAN 2009
- Received 31 July 1987, accepted for publication 15 February 1988
- Escherichia coli;
- meso-diaminopimelate-adding enzyme;
- synthetic inhibitors;
- transition-state analogs
In order to obtain inhibitors of the meso-diaminopimelate-adding enzyme, which participates in the biosynthesis of bacterial peptidoglycan, several Nα -propionyl-dipeptides of the general formula Pr-l-Ala-ambo-Xaa-OH were synthesized. Xaa represented methionine S,S-dioxide, methionine S-oxide, methionine sulfoximine, and 2-amino-4-phosphonobutyric acid, i.e. transition state analogs of glutamine synthetase and γ-glutamyl-cysteine synthetase, which catalyze the same type of reaction as our target enzyme. After synthesis, the diastereoisomers were separated by preparative HPLC or t.l.c.; those containing methionine derivatives could be identified thanks to previously synthesized reference compounds. After preincubation with the meso-diaminopimelate-adding activity from Escherichia coli. the ld diastereoisomers displayed moderate inhibitory effects, whereas the ll ones were inefficient. The best inhibition was obtained with one diastereoisomer of Pr-l-Ala-ζ-2-amino-4-phosphonobutyrate, presumably the ld one. A chloromethylketone derivative Pr-l-Ala-d-Glu(CH2Cl)-OH, potential affinity labeler of the meso-diaminopimelate-adding enzyme, was also synthesized. In the assay with preincubation, this compound behaved as the best inhibitor.