Identification and immunological evaluation of novel TLR2 agonists through structure optimization of PamCSK.
Bioorganic & Medicinal Chemistry(2019)
Abstract
•A novel series of Pam3CSK4 derivatives were designed, prepared, and evaluated for their immune-stimulatory activities based on the study of crystal structure of hTLR2-hTLR1-Pam3CSK4 complex.•Compound 35c was identified as a murine-specific TLR2 agonist, while 35f was a human-specific TLR2 agonist.•Compound 35d (human and murine TLR2 agonist) showed comparable TLR2 agonistic activity to Pam3CSK4.•Compounds 35a and 35d were TLR2/1 agonists, while 35f was a TLR2/6 agonist.
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Key words
TLR2 agonists,Pam3CSK4,Structure optimization,TLR2/1,TLR2/6
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