Further Insights on Structural Modifications of Muramyl Dipeptides to Study the Human NOD2 Stimulating Activity
Journal
Chemistry, an Asian journal
Journal Volume
15
Journal Issue
22
Pages
3836
Date Issued
2020-11-16
Author(s)
Cheng, Wei-Chieh
You, Ting-Yun
Teo, Zhen-Zhuo
Sayyad, Ashik A
Maharana, Jitendra
Guo, Chih-Wei
Lin, Chung-Shun
Meng, Fan-Chun
Abstract
A series of muramyl dipeptide (MDP) analogues with structural modifications at the C4 position of MurNAc and on the d-iso-glutamine (isoGln) residue of the peptide part were synthesized. The C4-diversification of MurNAc was conveniently achieved by using CuAAC click strategy to conjugate an azido muramyl dipeptide precursor with structurally diverse alkynes. d-Glutamic acid (Glu), replaced with isoGln, was applied for the structural diversity through esterification or amidation of the carboxylic acid. In total, 26 MDP analogues were synthesized and bio-evaluated for the study of human NOD2 stimulation activity in the innate immune response. Interestingly, MDP derivatives with an ester moiety are found to be more potent than reference compound MDP itself or MDP analogues containing an amide moiety. Among the varied lengths of the alkyl chain in ester derivatives, the MDP analogue bearing the d-glutamate dodecyl (C12) ester moiety showed the best NOD2 stimulation potency.
Subjects
Biological activity; Innate immunity; Muramyl dipeptide (MDP); NOD2; Peptidoglycan; Structure activity relationship
SDGs
Publisher
WILEY-V C H VERLAG GMBH