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Design, Synthesis, and Immunological Evaluation of Benzyloxyalkyl-Substituted 1,2,3-Triazolyl ?-GalCer Analogues.

ABSTRACT: Replacement of the amide moiety in the structure of ?-GalCer with a 1,2,3-triazole linker is known to elicit a response skewed toward Th2 immunity, and glycolipids containing an aromatic ring in the terminus of their acyl or phytosphingosine structural component exhibit an enhanced Th1 immune response. In the current study, synthesis and immunological screening of a focused library of benzyloxyalkyl-substituted 1,2,3-triazolyl ?-GalCer analogues are reported. The novel ?-GalCer analogues activate invariant natural killer T (iNKT) cells via CD1d mediated presentation, which was confirmed by in vitro tests performed on iNKT hybridomas incubated with CD1d proteins. When tested on isolated murine splenocytes, the T1204B and T1206B compounds stimulated higher levels of both IFN-? and IL-4 cytokine expression in vitro compared to that of ?-GalCer.

SUBMITTER: Verma YK

PROVIDER: S-EPMC4753537 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Design, Synthesis, and Immunological Evaluation of Benzyloxyalkyl-Substituted 1,2,3-Triazolyl α-GalCer Analogues.

Verma Yogesh Kumar YK Reddy Bonam Srinivasa BS Pawar Mithun S MS Bhunia Debabrata D Sampath Kumar Halmuthur M HM

ACS medicinal chemistry letters 20151210 2

Replacement of the amide moiety in the structure of α-GalCer with a 1,2,3-triazole linker is known to elicit a response skewed toward Th2 immunity, and glycolipids containing an aromatic ring in the terminus of their acyl or phytosphingosine structural component exhibit an enhanced Th1 immune response. In the current study, synthesis and immunological screening of a focused library of benzyloxyalkyl-substituted 1,2,3-triazolyl α-GalCer analogues are reported. The novel α-GalCer analogues activat ...[more]

PMID: 26985293

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