Multiple antigenic peptide, MAP

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. 

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. 

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... 

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. 

Several peptide dendrimers have been reported/ a major application of which is for the preparation of multiple antigen peptides (MAPs). For example, Tam used the poly (lysine) platform to prepare a MAP. These peptides are used to activate the immune system to produce large numbers of antipeptide antibodies, and their use avoids the immunogenicity and the other disadvantages associated with conventional antigenic systems. 

Aoki N, Mori M, Kato K, et al. Antibody against synthetic multiple antigen peptides (MAP) of JG virus capsid protein (VPl) without cross reaction to BK virus a diagnostic tool fot progressive multifocal leukoencephalopathy. Neurosci Lett. 1996 205 111-114. 

In Fmoc chemistry, Lys and Om are conveniently blocked with the Boc protecting group [155]. For more temporary protection, the l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) protecting group is useful in the preparation of branched peptides, multiple antigenic peptides (MAPs), cyclic peptides, template-assembled synthetic proteins (TASPs), and templates for combinatorial chemistry [156-161]. Dde is quasi-orthogonal because the use of dilute hydrazine to cleave Dde partially removes the A -... 

As well as by conjugation to a macromolecule, such as a protein, peptides can be presented as a larger construct in the form of a multiple antigen peptide (MAP). In this type of construct various copies of the peptide are attached to a small core structure (38). The construct, which is fully synthetic, is also known as a dendrimer (39). An MAP might contain one particular peptide (homo-MAP) or two (or even more) distinct peptides (hetero-MAP). MAPs can be prepared by direct sequential synthesis or by fragment condensation of modified peptides and an activated MAP core construct. 

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