Multiple antigen peptides

Other types of branched peptide dendrimers, known as multiple antigen peptides (MAPs), have been synthesized to mimic proteins for applications, for instance as synthetic vaccines, serodiagnostics, peptide inhibitors and intracellular delivery vehicles. Since this concept has been recently described in detail elsewhere [11], only the conceptual framework will be briefly presented here. Tam and coworkers have developed a dendritic core based on lysine units for the construction of MAPs [12-15] (Fig. 3). Carrying antigens at their periphery these MAPs have been designed to increase antigenicity and immunogenicity of peptides. 

Tam, J.P. (1988) Synthetic peptide vaccine design Synthesis and properties of a high-density multiple antigenic peptide system. Proc. Natl. Acad. Sci. USA 85, 5409-5413. 

Applications of the TASP approach are then considered for such aspects as four-helical bundles (Section 13.1.2.4.2)J4 The details of structures and synthetic routes for the preparation of the bundles are described. Other chain assemblies and applications are discussed (Section 13.1.2.5) including metal-ion assisted self assemblies, disulfide linkages in the formation of four-helical bundles (Section 13.1.2.5.2), multiple antigenic peptide systems (Section 13.1.2.5.4), and templates constructed from a trialdehyde template by reductive amination to form a three-helical bundle (Section 13.1.2.5.5))5 ... 

High-Density Multiple Antigenic Peptide Systems... 

Scheme 2 Left Schematic Representation of a Multiple Antigen Peptide (MAP), Consisting of Eight Peptide Monomers and a Di-K2K Dendron. Right Successive Generations of a Lys Branching Unit to Afford Various K2K Dendrons and Surface Amine Groups...

A unique synthetic molecule that can be used as a carrier is the so-called multiple antigenic peptide (MAP) (Tam, 1988 Bosnetteta/., 1988). The MAP core structure is composed of a scaffolding of sequential levels of poly-L-lysine. The matrix is constructed from a divalent lysine compound to which two additional levels of lysine are attached. The final MAP compound consists of a symmetrical, octavalent primary... 

Ferru, I., Georges, B., Bossus, M., Estaquier, J., Delacre, M., Harn, D.A., Tartar, A., Capron, A., Grassmasse, H. and Auriault, C. (1 997) Analysis of the immune response elicited by a multiple antigen peptide (MAP) composed of two distinct protective antigens derived from the parasite Schistosoma mansoni. Parasite Immunology 19, 1-11. 

Reynolds, S.R., Dahl, C.E. and Harn, D.A. (1 994)T and B epitope determination and analysis of multiple antigenic peptides for the Schistosoma mansoni experimental vaccine triose-phosphate isomerase. The Journal of Immunology 1 52, 1 93-200. 

The synthesis of the branched core of the lipid headgroups [24, 45] proceeds in the same manner as that of multiple antigenic peptides (MAPs) [50, 51 ] or polyethylene glycol-dendritic oligo-lysine block copolymers [52]. It starts from ornithine... 

Mozdzanowska, K., Feng, J., Eid, M et al. (2003) Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2. Vaccine 21, 2616-2626. 

Pessi et al. 68 prepared a different multiple antigen peptide employing the continuous-flow polypeptide procedure 69 for the solid-phase peptide synthesis. The resultant one-directional, octaantigen, polypeptide cascade 37 is depicted in Figure 4.2 and was characterized by gel permeation chromatography (GPC), FAB MS, and amino acid ratio analysis. 

Coupling of lipids to peptide antigens may be performed directly or via an amplifying dendrimer carrier system. A commonly investigated carrier is the multiple antigen peptide (MAP)-system, which connects peptide antigens through a branched polylysine core. 

Fig. 26. An octameric multiple antigen peptide grafted to the surface of a poly(lysine) monodendron...

Ziegler J, Change R, Wright D. Multiple-antigenic peptides of histidine-rich protein 11 of Plasmodium falciparum den-drimeric biomineralization template. J. Am. Chem. Soc. 1999 121 2395-2400. 

We have demonstrated that peptides which differ in their C-tennini can be simultaneously synthesized in one reaction vessel by employing resins that possess different cleavage properties. This synthesis, strategy can also be used for the synthesis of multiple antigenic peptide systems, MAPS (8) and their corresponding des-lysine core sequences. Moreover, this strategy can be expanded to the synthesis of more than two peptides by employing other resins such as the HF cleavable Pam resins and the photo-labile resins. 

---