Display options
Cite
Verma YK, Reddy BS, Pawar MS, et al. Design, Synthesis, and Immunological Evaluation of Benzyloxyalkyl-Substituted 1,2,3-Triazolyl α-GalCer Analogues. ACS Med Chem Lett. 2015;7(2):172-6doi: 10.1021/acsmedchemlett.5b00340.
Verma, Y. K., Reddy, B. S., Pawar, M. S., Bhunia, D., & Sampath Kumar, H. M. (2016). Design, Synthesis, and Immunological Evaluation of Benzyloxyalkyl-Substituted 1,2,3-Triazolyl α-GalCer Analogues. ACS medicinal chemistry letters, 7(2), 172-6. https://doi.org/10.1021/acsmedchemlett.5b00340
Verma, Yogesh Kumar, et al. "Design, Synthesis, and Immunological Evaluation of Benzyloxyalkyl-Substituted 1,2,3-Triazolyl α-GalCer Analogues." ACS medicinal chemistry letters vol. 7,2 (2016): 172-6. doi: https://doi.org/10.1021/acsmedchemlett.5b00340
Verma YK, Reddy BS, Pawar MS, Bhunia D, Sampath Kumar HM. Design, Synthesis, and Immunological Evaluation of Benzyloxyalkyl-Substituted 1,2,3-Triazolyl α-GalCer Analogues. ACS Med Chem Lett. 2015 Dec 10;7(2):172-6. doi: 10.1021/acsmedchemlett.5b00340. eCollection 2016 Feb 11. PMID: 26985293; PMCID: PMC4753537.
Copy Download .nbib Format: NLM
Share it on

ACS Med Chem Lett. 2015 Dec 10;7(2):172-6. doi: 10.1021/acsmedchemlett.5b00340. eCollection 2016 Feb 11.

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

ACS medicinal chemistry letters

Yogesh Kumar Verma, Bonam Srinivasa Reddy, Mithun S Pawar, Debabrata Bhunia, Halmuthur M Sampath Kumar

Affiliations

  1. Vaccine Immunology Laboratory, Natural Products Chemistry Division, Indian Institute of Chemical Technology , Hyderabad 500007, India.
  2. Vaccine Immunology Laboratory, Natural Products Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.

PMID: 26985293 PMCID: PMC4753537 DOI: 10.1021/acsmedchemlett.5b00340

Abstract

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 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-γ and IL-4 cytokine expression in vitro compared to that of α-GalCer.

Keywords: IFN-γ; IL-4; Th1/Th2; benzyloxyalkyl α-GalCer; iNKT hybridoma; kinetic release

References

  1. Nat Rev Immunol. 2004 Mar;4(3):231-7 - PubMed
  2. Nat Rev Immunol. 2012 Feb 17;12(3):180-90 - PubMed
  3. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):3972-7 - PubMed
  4. Clin Cancer Res. 2002 Dec;8(12):3702-9 - PubMed
  5. Org Lett. 2005 May 12;7(10):2063-5 - PubMed
  6. J Org Chem. 2010 Aug 6;75(15):4891-8 - PubMed
  7. Am J Respir Crit Care Med. 2010 Sep 15;182(6):841-7 - PubMed
  8. Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3383-8 - PubMed
  9. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13010-5 - PubMed
  10. Nature. 2001 Oct 4;413(6855):531-4 - PubMed
  11. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10299-304 - PubMed
  12. J Med Chem. 1995 Jun 9;38(12):2176-87 - PubMed
  13. Org Biomol Chem. 2011 May 7;9(9):3080-104 - PubMed
  14. Clin Immunol. 2011 Aug;140(2):142-51 - PubMed
  15. Bioorg Med Chem. 2014 Oct 1;22(19):5279-89 - PubMed
  16. EMBO J. 2011 Jun 1;30(11):2294-305 - PubMed
  17. Vaccine. 2008 Mar 28;26(15):1807-16 - PubMed
  18. J Nat Prod. 2001 Sep;64(9):1210-5 - PubMed
  19. C R Chim. 2012 Jan 1;15(1):46-56 - PubMed
  20. Curr Med Chem. 2004 Jan;11(2):241-52 - PubMed
  21. Chem Biol. 2011 Dec 23;18(12):1620-30 - PubMed
  22. J Exp Med. 2002 Mar 4;195(5):617-24 - PubMed
  23. Curr Opin Immunol. 2008 Jun;20(3):358-68 - PubMed
  24. J Med Chem. 2007 Feb 8;50(3):585-9 - PubMed
  25. Molecules. 2013 Sep 12;18(9):11198-218 - PubMed
  26. Immunol Today. 2000 Nov;21(11):573-83 - PubMed
  27. Nat Rev Immunol. 2005 Jan;5(1):31-42 - PubMed
  28. J Med Chem. 2006 Sep 21;49(19):5830-9 - PubMed

Publication Types