Development of N-acetylated dipalmitoyl-S-glyceryl cysteine analogs as efficient TLR2/TLR6 agonists

Yang Zhou, Abid H. Banday, Victor J. Hruby, Minying Cai

Research output: Contribution to journalArticle

Abstract

Cancer vaccine is a promising immunotherapeutic approach to train the immune system with vaccines to recognize and eliminate tumors. Adjuvants are compounds that are necessary in cancer vaccines to mimic an infection process and amplify immune responses. The Toll-like receptor 2 and 6 (TLR2/TLR6) agonist dipalmitoyl-S-glyceryl cysteine (Pam2Cys) was demonstrated as an ideal candidate for synthetic vaccine adjuvants. However, the synthesis of Pam2Cys requires expensive N-protected cysteine as a key reactant, which greatly limits its application as a synthetic vaccine adjuvant in large-scaled studies. Here, we report the development of N-acetylated Pam2Cys analogs as TLR2/TLR6 agonists. Instead of N-protected cysteine, the synthesis utilizes N-acetylcysteine to bring down the synthetic costs. The N-acetylated Pam2Cys analogs were demonstrated to activate TLR2/TLR6 in vitro. Moreover, molecular docking studies were performed to provide insights into the molecular mechanism of how N-acetylated Pam2Cys analogs bind to TLR2/TLR6. Together, these results suggest N-acetylated Pam2Cys analogs as inexpensive and promising synthetic vaccine adjuvants to accelerate the development of cancer vaccines in the future.

Original languageEnglish (US)
Article number3512
JournalMolecules
Volume24
Issue number19
DOIs
StatePublished - Sep 27 2019

Fingerprint

vaccines
cysteine
analogs
Cancer Vaccines
Synthetic Vaccines
cancer
Cysteine
Toll-Like Receptor 6
Toll-Like Receptor 2
immune systems
Immune system
Acetylcysteine
infectious diseases
synthesis
S-(2,3-bis(palmitoyloxy)propyl)cysteine
Tumors
Immune System
tumors
Vaccines
costs

Keywords

  • Adjuvant
  • Cancer vaccine
  • N-acetylated PamCys
  • PamCys
  • Synthetic vaccine
  • Toll-like receptor

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Development of N-acetylated dipalmitoyl-S-glyceryl cysteine analogs as efficient TLR2/TLR6 agonists. / Zhou, Yang; Banday, Abid H.; Hruby, Victor J.; Cai, Minying.

In: Molecules, Vol. 24, No. 19, 3512, 27.09.2019.

Research output: Contribution to journalArticle

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