Design, synthesis and immunological evaluation of 1,2,3-triazole-tethered carbohydrate-Pam3Cys conjugates as TLR2 agonists

Naresh Nalla, Preethi Pallavi, Bonam Srinivasa Reddy, Sreekanth Miryala, V. Naveen Kumar, Mohammed Mahboob, M. Sampath Kumar Halmuthur

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Novel triazolyl Pam3Cys conjugates encompassing various carbohydrate entities have been synthesized by copper mediated azide-alkyne click chemistry protocol with a view to probe the SAR pertaining to their adjuvant activity in conjunction with OVA as antigen. The preliminary ex vivo cytokine profiling revealed optimal Th1 activation and the in vivo adjuvant studies of ribose derived hybrid (6e) revealed a marked improvement in the OVA specific antibody IgG response and Th1 cytokine expressions. The triazolyl Pam3Cys carbohydrate conjugates were found to be the hTLR2 agonists as revealed by their SEAP activity due to NFKB activation. The described protocol is the first successful attempt of the amalgamation of carbohydrate-Pam3Cys motifs tethered to a triazole linker as a peptide free adjuvant.

Original languageEnglish (US)
Pages (from-to)5846-5855
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume23
Issue number17
DOIs
StatePublished - May 25 2015
Externally publishedYes

Keywords

  • Adjuvants
  • Carbohydrate
  • Click chemistry
  • Cytokines
  • PamCys

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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