Ten-membered rings as key interaction motifs in folding of desmuramyl di-, tri-, and tetrapeptides

Muropeptides are fragments of polymeric peptidoglycan, unique constituent of bacterial cell walls, acting as immunostimulators (adjuvants). The smallest biologically active unit of peptidoglycan is N-acetylmuramyl-L-alanyl-D-isoglutamine. In this paper, the synthesis and conformational analysis of desmuramyl peptides, derivatives lacking the N-acetylmuramyl moiety, is described. Systematic conformational analysis (bottom-up approach) of peptides in zwitterionic and non-zwitterionic forms of corresponding desmuramyl di-, tri-, and tetrapeptides was performed and results were compared with experimental data obtained by NMR study. Ten-membered ring (C10, N 1b H⋯O 3 ) formed between isoGln amide group and C=O of AdGly was found to be a key interaction that constitutes the central structural spine and initiates β-turn-like folding in our model peptide systems.