Assembly of Peptidoglycan Fragments—A Synthetic Challenge

Abstract

Peptidoglycan (PGN) is a major constituent of most bacterial cell walls that is recognized as a primary target of the innate immune system. The availability of pure PGN molecules has become key to different biological studies. This review aims to (1) provide an overview of PGN biosynthesis, focusing on the main biosynthetic intermediates; (2) focus on the challenges for chemical synthesis posed by the unique and complex structure of PGN; and (3) cover the synthetic routes of PGN fragments developed to date. The key difficulties in the synthesis of PGN molecules mainly involve stereoselective glycosylation involving NAG derivatives. The complex synthesis of the carbohydrate backbone commonly involves multistep sequences of chemical reactions to install the lactyl moiety at the O-3 position of NAG derivatives and to control enantioselective glycosylation. Recent advances are presented and synthetic routes are described according to the main strategy used: (i) based on the availability of starting materials such as glucosamine derivatives; (ii) based on a particular orthogonal synthesis; and (iii) based on the use of other natural biopolymers as raw materials.

Recent Advances in the Synthesis and Biological Applications of Peptidoglycan Fragments

“…Concurrent with the writing of this review the Marques and Filipe groups published a review outlining advances in the chemical synthesis of peptidoglycan fragments [15] . While their review presents a thorough outline of this topic, it is limited to this one area of research.…”

“…Concurrent with the writing of this review the Marques and Filipe groups published a review outlining advances in the chemical synthesis of peptidoglycan fragments. [15] While their review presents a thorough outline of this topic, it is limited to this one area of research. This review encapsulates a much greater breadth of subjects and covers topics such as the synthesis of muramyl dipeptides (MDPs), Park's nucleotides, PG lipids, orthogonally-protected meso-Dap, and anhydro-PG fragments.…”