Amino Acids

, Volume 39, Issue 2, pp 471–480 | Cite as

Structural requirement for the agonist activity of the TLR2 ligand Pam2Cys

  • Weiguang ZengEmail author
  • Emily Eriksson
  • Brendon Chua
  • Lara Grollo
  • David C. JacksonEmail author
Original Article


Synthetic lipopeptides have demonstrated great potential as a vaccine strategy for eliciting cellular and humoral immunity. One of the most potent lipid moieties used is S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam2Cys). Pam2Cys binds to and activates dendritic cells by engagement of Toll like receptor 2 (TLR 2). In this study, we have investigated the structural requirement of the agonist activity of Pam2Cys by varying the three structural elements of the core structure S-(2,3-dihydroxypropyl)-cysteine namely (1) the α-amino group of the cysteine residue (2) the sulphur atom of the cysteine residue and (3) the 2,3-dihydroxypropyl moiety. Four novel analogues of Pam2Cys were made and each of these analogues were incorporated into vaccine constructs and examined for immunogenicity. Our results demonstrate that (1) the potency of the peptide vaccine is least affected by removal of the amino group (2) substitution of the sulphur atom with an amide bond leads to significant reduction of biological activity (3) removal of the amino group and at the same time substitution of the sulphur with an amide bond significantly decreases the biological activity (4) in the two analogues in which the sulphur atom is replaced with an amide bond the analogue containing the 1,3-dihydroxypropyl moiety demonstrates higher activity than the one which contains 2,3-dihydroxypropyl. In conclusion, the results demonstrate strict structural requirements for agonist activity of the TLR2 ligand Pam2Cys.


Vaccine Peptide TLR2 Structure–activity relationship Lipopeptide 



This work was supported by grant from the National Health and Medical Research Council of Australia.


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of Microbiology and ImmunologyThe University of MelbourneParkvilleAustralia

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