Abstract:
TLR2 agonists are at the forefront of vaccine research for a plethora of diseases, in particular they offer a promising tool for the treatment of cancer. A detailed knowledge of their structure–activity relationship informs the methodical design of vaccine constructs that include TLR2 agonists. Herein we report the design, synthesis, and biological evaluation of analogues of the TLR2 agonist Pam2Cys to further probe structure–activity relationships. These analogues replace one or other of the two ester groups with ether functionalities to elucidate the role of the carbonyls on TLR2 activity. Through this we demonstrate that the C3 ester carbonyl is dispensable, but the C2 carbonyl is essential for activity.
