Peptides Containing meso-Oxa-Diaminopimelic Acid as Substrates for the Cell Shape-Determining Proteases Csd6 and Pgp2.

Peptides Containing meso-Oxa-Diaminopimelic Acid as Substrates for the Cell Shape-Determining Proteases Csd6 and Pgp2. Chembiochem. 2019 Feb 11;: Authors: Soni A, Lin C, Murphy M, Tanner ME Abstract The enzymes Csd6 and Pgp2 are peptidoglycan (PG) proteases found in the pathogenic bacteria Helicobacter pylori and Campylobacter jejuni, respectively. These enzymes are involved in the trimming of uncrosslinked PG sidechains and catalyze the cleavage of the bond between meso-diaminopimelic acid (meso-Dap) and D-alanine, thus converting a PG-tetrapeptide into a PG-tripeptide. They are known to be cell shape-determining enzymes, since deletion of the corresponding genes result in mutant strains that have lost the normal helical phenotype and instead possess a straight rod morphology. In this work, we report two approaches towards the synthesis of a tripeptide substrate, Ac-iso-D-Glu-meso-oxa-Dap-D-Ala, that serves as a mimic of the terminus of an uncrosslinked PG-tetrapeptide substrate. The isosteric analog meso-oxa-Dap is utilized in place of meso-Dap to simply the synthetic procedure. The more efficient synthesis involves the ring opening of a peptide-embedded aziridine by a serine-based nucleophile. A branched tetrapeptide is also prepared as a mimic of the terminus of a crosslinked PG-tetrapeptide. We use a mass spectral analysis to demonstrate that the tripeptide serves as a substrate for both Csd6 and Pgp2, and that the branched tetr...
Source: Chembiochem - Category: Biochemistry Authors: Tags: Chembiochem Source Type: research