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


METHODS
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 as1H NMR, STD NMR, DOSY and Molecular docking.


RESULTS
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.
Division of Molecular Medicine, Bose Institute, P-1/12, C.I.T. Scheme VII (M), Kolkata 700054, India.
Manas
M
Jana
Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700054, India.
Anirban
A
Ghosh
Division of Molecular Medicine, Bose Institute, P-1/12, C.I.T. Scheme VII (M), Kolkata 700054, India.
Abhishek
A
Santra
Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700054, India.
Rajiv Kumar
RK
Kar
Division of Molecular Medicine, Bose Institute, P-1/12, C.I.T. Scheme VII (M), Kolkata 700054, India. Electronic address: akmisra69@gmail.com.
Anup Kumar
AK
Misra
Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700054, India. Electronic address: anirbanbhunia@gmail.com.
Anirban
A
Bhunia
D001665:Binding Sites; D062105:Molecular Docking Simulation; D009112:Muramic Acids / Q000737:chemistry*; D009113:Muramidase / Q000737:chemistry*; D010457:Peptidoglycan / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D009112:Muramic Acids; D010457:Peptidoglycan; D009113:Muramidase
Amide; Glycomimetics; Lysozyme; Molecular docking; Muramic acid; STD NMR