Peptide-Based Drug Design

14
Synthesis of Toll-Like Receptor-2 Targeting Lipopeptides
as Self-Adjuvanting Vaccines
Brendon Y. Chua, Weiguang Zeng, and David C. Jackson
Summary
Effective Th1- and Th2-type immune responses that result in protective immunity
against pathogens can be induced by self-adjuvanting lipopeptides containing the
lipid moiety dipalmitoyl-S-glyceryl cysteine (Pam2Cys). The potent immunogenicity of
these lipopeptides is due to their ability to activate dendritic cells by targeting and
signaling through Toll-like receptor-2 (TLR-2). In addition, the simplicity and flexibility
in their design as well as their ease of chemical definition and characterisation
makes them highly attractive vaccine candidates for humans and animals. We
describe in this chapter the techniques involved in the synthesis of an immunocontraceptive
lipopeptide vaccine as well as the experimental assays carried out to evaluate its
efficiency.
Key Words: Self-adjuvanting lipopeptide; peptide synthesis; ELISA; antibody;
immunocontraception.
1. Introduction
Immunization with peptide epitopes in adjuvant can elicit both antibodyand
cellular-mediated immune responses that are able to provide protective
immunity against a repertoire of targeted pathogens that have included viruses
(1–4), bacteria (4–7), parasites (4,8–10), tumors (11–14), and self-hormones
(4,15–18). However, a major problem associated with the use of subunit
From: Methods in Molecular Biology, vol. 494: Peptide-Based Drug Design
Edited by: L. Otvos, DOI: 10.1007/978-1-59745-419-3 14, © Humana Press, New York, NY
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