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

doi:10.1016/j.bmc.2015.06.070

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 journal › Article › peer-review

17 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 language	English (US)
Pages (from-to)	5846-5855
Number of pages	10
Journal	Bioorganic and Medicinal Chemistry
Volume	23
Issue number	17
DOIs	https://doi.org/10.1016/j.bmc.2015.06.070
State	Published - May 25 2015
Externally published	Yes

Keywords

Adjuvants
Carbohydrate
Click chemistry
Cytokines
PamCys

ASJC Scopus subject areas

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

Access to Document

10.1016/j.bmc.2015.06.070

Cite this

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

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.",

keywords = "Adjuvants, Carbohydrate, Click chemistry, Cytokines, PamCys",

author = "Naresh Nalla and Preethi Pallavi and Reddy, {Bonam Srinivasa} and Sreekanth Miryala and {Naveen Kumar}, V. and Mohammed Mahboob and Halmuthur, {M. Sampath Kumar}",

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AU - Nalla, Naresh

AU - Pallavi, Preethi

AU - Reddy, Bonam Srinivasa

AU - Miryala, Sreekanth

AU - Naveen Kumar, V.

AU - Mahboob, Mohammed

AU - Halmuthur, M. Sampath Kumar

PY - 2015/5/25

Y1 - 2015/5/25

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