Synthesis and biological evaluation of novel 2-azido muramyl dipeptide as NOD2 agonistic adjuvants

Paturu Rama Subba Reddy; Shainy Sambyal; Tukaram B Mhamane; Vemireddy Sravanthi; Syed Shafi; Imran A Khan; Halmuthur M Sampath Kumar

doi:10.1016/j.bmc.2022.116781

Synthesis and biological evaluation of novel 2-azido muramyl dipeptide as NOD2 agonistic adjuvants

Bioorg Med Chem. 2022 Jul 15:66:116781. doi: 10.1016/j.bmc.2022.116781. Epub 2022 May 2.

Authors

Paturu Rama Subba Reddy¹, Shainy Sambyal¹, Tukaram B Mhamane¹, Vemireddy Sravanthi², Syed Shafi³, Imran A Khan³, Halmuthur M Sampath Kumar⁴

Affiliations

¹ Vaccine Immunology Laboratory, OSPC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201 002, India.
² Vaccine Immunology Laboratory, OSPC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
³ Department of Chemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India.
⁴ Vaccine Immunology Laboratory, OSPC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201 002, India. Electronic address: sampath.iict@gov.in.

PMID: 35569249
DOI: 10.1016/j.bmc.2022.116781

Abstract

Novel 2-Azido muramyl dipeptide was synthesized by the bio-isosteric replacement of the N-acetyl group of the muramic acid fragment with the azide functionality at the C2 position. In order to examine the effect of hydrophilic-lipophilic balance on the adjuvant activity, derivatives were synthesized by removing protecting groups sequentially to tune the polarity. Amongst five novel azido derivatives of MDP studied here, di- and mono-benzylated azido derivatives 10 and 11 exhibited good DENV specific antibody(IgG) response with Th1 polarization compared to parent compound Muramyl dipeptide (MDP) whereas all five new derivatives responded positively to NOD2 agonistic assays with compound 10 showing highest stimulation.

Keywords: 2-AZMDP(1-5); Bio-isosters; CD4; CD8; DENV; MDP; NOD2 agonist.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylmuramyl-Alanyl-Isoglutamine* / pharmacology
Adjuvants, Immunologic / chemistry
Adjuvants, Pharmaceutic
Hydrophobic and Hydrophilic Interactions
Nod2 Signaling Adaptor Protein*

Substances

Adjuvants, Immunologic
Adjuvants, Pharmaceutic
Nod2 Signaling Adaptor Protein
Acetylmuramyl-Alanyl-Isoglutamine