Thioester analogues of peptidoglycan fragment MurNAc-L-Ala-γ-D-Glu as substrates for peptidoglycan hydrolase MurNAc-L-Ala amidase

MurNAc-L-amidase is one of a family of peptidoglycan hydrolases which catalyses the breakdown of bacterial peptidoglycan. Analogues of the peptidoglycan fragment MurNAc-L-Ala- gamma -D-Glu containing S-thiolactic acid in place of L-alanine were synthesised as thioester substrates for this enzyme. Tr...

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Bibliographic Details
Published in:Perkin 1 : an international journal of organic and bio-organic chemistry 2002-07 (14), p.1714-1722
Main Authors: Harding, Ross L., Henshaw, Joanne, Tilling, Joannah, Bugg, Timothy D. H.
Format: Article
Language:English
Subjects:
Bacteriophages
Catalysis
Enzymes
Molecular structure
Stereochemistry
Synthesis (chemical)
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Summary:MurNAc-L-amidase is one of a family of peptidoglycan hydrolases which catalyses the breakdown of bacterial peptidoglycan. Analogues of the peptidoglycan fragment MurNAc-L-Ala- gamma -D-Glu containing S-thiolactic acid in place of L-alanine were synthesised as thioester substrates for this enzyme. Triphenylmethanethiol was used to develop a stereoselective synthesis of S-thiolactic acid, which was elaborated synthetically into MurNAc-dipeptide analogues. MurNAc-S-thioacetyl-N-propylamide 13 and MurNAc-S-thiolactyl-2R-alaninamide 16 were found not to be substrates for recombinant MurNAc-L-Ala amidases CwlA from Bacillus subtilis and Ply21 from bacteriophage TP21, however, turnover of tripeptide thioester S-propionylthiolactyl- gamma -D-Glu-L-Lys-OMe 21 was observed using amidase Ply21. Therefore, recognition of the amino acid at position 3 of the pentapeptide sidechain appears to be important for enzymatic turnover.
ISSN:1472-7781
1364-5463
DOI:10.1039/b200921h