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

摘要

MurNAc--amidase is one of a family of peptidoglycan hydrolases which catalyses the breakdown of bacterialnpeptidoglycan. Analogues of the peptidoglycan fragment MurNAc--Ala-γ--Glu containing S-thiolactic acidnin place of -alanine were synthesised as thioester substrates for this enzyme. Triphenylmethanethiol was used tondevelop a stereoselective synthesis of S-thiolactic acid, which was elaborated synthetically into MurNAc-dipeptidenanalogues. MurNAc-S-thioacetyl-N-propylamide 13 and MurNAc-S-thiolactyl-2R-alaninamide 16 were found notnto be substrates for recombinant MurNAc--Ala amidases CwlA from Bacillus subtilis and Ply21 from bacteriophagenTP21, however, turnover of tripeptide thioester S-propionylthiolactyl-γ--Glu--Lys-OMe 21 was observed usingnamidase Ply21. Therefore, recognition of the amino acid at position 3 of the pentapeptide sidechain appears to benimportant for enzymatic turnover.