Synthesis of novel muramic acid derivatives and their interaction with lysozyme: Action of lysozyme revisited

Manas Jana; Anirban Ghosh; Abhishek Santra; Rajiv Kumar Kar; Anup Kumar Misra; Anirban Bhunia

doi:10.1016/j.jcis.2017.03.060

Synthesis of novel muramic acid derivatives and their interaction with lysozyme: Action of lysozyme revisited

J Colloid Interface Sci. 2017 Jul 15:498:395-404. doi: 10.1016/j.jcis.2017.03.060. Epub 2017 Mar 16.

Authors

Manas Jana¹, Anirban Ghosh², Abhishek Santra¹, Rajiv Kumar Kar², Anup Kumar Misra³, Anirban Bhunia⁴

Affiliations

¹ Division of Molecular Medicine, Bose Institute, P-1/12, C.I.T. Scheme VII (M), Kolkata 700054, India.
² Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700054, India.
³ Division of Molecular Medicine, Bose Institute, P-1/12, C.I.T. Scheme VII (M), Kolkata 700054, India. Electronic address: akmisra69@gmail.com.
⁴ Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700054, India. Electronic address: anirbanbhunia@gmail.com.

PMID: 28343137
DOI: 10.1016/j.jcis.2017.03.060

Abstract

Hypothesis: The interaction of lysozyme with the N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) unit of peptidoglycan (PGN) polymer of the bacterial cell wall is of immense importance to understand the mechanism of lysozyme on PGN.

Experiments: The synthesis of three novel NAM derivatives containing fused oxazinone ring to the NAM moiety has been achieved. The synthesized compounds were evaluated for their potential as a glycomimetic acceptor of lysozyme using different biophysical and computational methods such as ¹H NMR, STD NMR, DOSY and Molecular docking.

Findings: Novel modified muramic acid derivatives have been synthesized in excellent yield containing fused cyclooxazine ring embedded on the muramic acid moiety using a newly developed hydrazinolysis reaction condition. From various biophysical studies, it has been established that the compound containing endo modified muramic acid moiety (compound 1) shows significant binding property for the lysozyme while the other isomer (compound 2) did not bind to the lysozyme. The catalytic residues Glu35 and Asp52 were found to be in the close proximity for the active molecule which justifies the selectivity of this molecule in conjunction to lysozyme enzymatic activity.

Keywords: Amide; Glycomimetics; Lysozyme; Molecular docking; Muramic acid; STD NMR.

MeSH terms

Binding Sites
Molecular Docking Simulation
Muramic Acids / chemistry*
Muramidase / chemistry*
Peptidoglycan / chemistry
Protein Binding
Protein Conformation
Structure-Activity Relationship

Substances

Muramic Acids
Peptidoglycan
Muramidase