Recent Advances in the Synthesis and Biological Applications of Peptidoglycan Fragments

Abstract

The biosynthesis, breakdown, and modification of peptidoglycan (PG) play vital roles in both bacterial viability and in the response of human physiology to bacterial infection. Studies on PG biochemistry are hampered by the fact that PG is an inhomogeneous insoluble macromolecule. Chemical synthesis is therefore an important means to obtain PG fragments that may serve as enzyme substrates and elicitors of the human immune response. This review outlines the recent advances in the synthesis and biochemical studies of PG fragments, PG biosynthetic intermediates (such as Park's nucleotides and PG lipids), and PG breakdown products (such as muramyl dipeptides and anhydro‐muramic acid‐containing fragments). A rich variety of synthetic approaches has been applied to preparing such compounds since carbohydrate, peptide, and phospholipid chemical methodologies must all be applied.

Mechanistic Insights into the Activities of Major Families of Enzymes in Bacterial Peptidoglycan Assembly and Breakdown

“…As a result, the full reconstitution of bacterial TPs has significantly lagged the characterisation of PGTs in the past decades. In recent years, the scarce Lipid II substrates have been made available through chemical synthesis [46,79,80] or extraction methods. [81] Analysis with state-of-the-art LC-MS has replaced traditional HPLC-based assays to enable facile detection of crosslinked peptidoglycan products.…”

Current Progress in the Chemoenzymatic Synthesis of Natural Products

“…The range in size from small monosaccharides to enormous polysaccharides possessing hundreds of glycan units correlates with their variety of biological targets and purposes of sugars. Given their versatility, they are used in multiple fields such as food chemistry, medicinal chemistry, and investigations of fundamental biological processes [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ].…”

Synthesis and validation of click-modified of NOD1/2 agonists

“…Howard Hang and co-workers used a similar approach in their synthesis of chemo-proteomic PGN probes [27], combining photoactivatable crosslinkers with a clickable alkyne moiety; while others have used solid phase synthesis to incorporate click probes on PGNs [28]. A recent review from Tanner and co-workers succinctly highlights our and others' synthetic efforts in this space [29].…”