Synthesis and biological application of a short peptidomimetics based on bacterial cell wall peptidoglycan monomer

Bacterial peptidoglycan (PG) (Figure 1.) plays a vital role in both bacterial viability and in the response of human physiology to bacterial infection.A large number of novel synthetic compounds representing smaller parts of original peptidoglycan molecules have been synthesized and found to possess versatile biological activity [1].Peptidoglycan monomer (PGM) was isolated from the cell wall of the non-pathogenic bacterium B. divaricatum by a procedure described in the literature, and its significant immunomodulating activity was confirmed [2].It was previously reported that bacterial cell wall fragments play important roles in the immune response of higher organisms against bacterial infections, and mediate the innate immune response.Furthermore, it is known that bacterial cell wall biosynthesis is a major target of antibiotics, including betalactam and glycopeptide antibiotics, such as vancomycin, which represent the last line of defense against antimicrobial resistance (AMR).Hence, based on the facts that peptides are increasingly becoming key therapeutic agents for a wide range of applications and that the introduction of triazolyl or lipidic moieties into the peptides as well as cyclization could stabilize the molecule to hydrolysis, oxidation, or reduction [3], the new PGM peptidomimetics are designed.The structure and conformation of the PGM molecule in solution, in DMSO, and in an aqueous medium, were studied in detail through molecular modeling and chemical calculations and were confirmed by 1 H NMR spectroscopy [4] (Figure 2.).Numerous PGM derivatives with an adamantane moiety, the amino acid tyrosine [5], and adamantyltripeptides have been synthesized.All the derivatizations were performed on the amino group present in the side chain of diaminopimelic acid.Still, no cyclic derivative has been synthesized, nor has a new functional group been introduced to the C-terminal end of the peptide.