Synthesis of inhibitors of the meso-diaminopimelate-adding enzyme from Escherichia coli
| Autor: | Didier Blanot, Martin Flegel, Mohamed Abo‐Ghalia, Jean van Heijenoort |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
chemistry.chemical_classification
Methionine biology Stereochemistry Affinity label Affinity Labels Stereoisomerism Dipeptides Biochemistry Ligases chemistry.chemical_compound Enzyme chemistry Biosynthesis Transition state analog Enzyme inhibitor Glutamine synthetase Escherichia coli biology.protein Peptidoglycan Peptide Synthases |
| Zdroj: | International Journal of Peptide and Protein Research. 32:208-222 |
| ISSN: | 0367-8377 |
| Popis: | In order to obtain inhibitors of the meso-diaminopimelate-adding enzyme, which participates in the biosynthesis of bacterial peptidoglycan, several N alpha-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 gamma-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-zeta-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|