Synthesis of multiple antigenic peptides (MAPs)—strategies and limitations

Abstract

Dendrimeric platforms such as MAPs can be synthesized either entirely by solid-phase methods (SPPS, direct approach) or by conjugation in solution of preformed, SPPS-made building blocks (indirect approach). Although MAPs and MAP-like constructs have been extensively and successfully used for various biological (mainly immunological) applications, experimental reports are most often lacking in chemical detail about their preparation and characterization. Here, we provide complete accounts of the synthesis and analytical documentation of MAPs and similar dendrimers by either all-SPPS (direct) or chemoselective thioether ligation (indirect) methods. We have chosen as model epitopes a 24-residue sequence of the ectodomain of protein M2 from influenza virus (M2e), which is found to be a rather challenging peptide epitope, and a far more manageable, shortened (12-residue) version of the same peptide. The advantages and shortcomings of both direct and indirect methods are discussed.

Evaluation of Multiple Antigenic Peptides Based on the Chikungunya E2 Protein for Improved Serological Diagnosis of Infection

“…MAP offers several advantages such as simple and convenient in design and synthesis (20), can be designed for multiple epitopes or multiple copies of a single epitope (36), highly immunogenic and antigenic, has a protein-like globular structure, noncytotoxic, biocompatible, resistant to proteolysis, easy standardization (2), and a multimeric nature, which provides reproducible result and increases surface binding. So MAP has been studied as an alternate source of antigen exploited for diagnosis (12).…”

Branched polymer models and the mechanism of multilayer film buildup

“…Both species of dendrimer were deposited at the same molality, that is, the same concentration of lysine residues. The number density of dendrimers in solution was therefore about half as much for 8-K 30 as 4-K 30 . The driving force for adsorption of 8-K 30 was lower from the point of view of particle chemical potential.…”

“…More branches will also have enabled bound dendrimers to bind more linear polyanion. There were twice as many branches in 8-K 30 as 4-K 30 , and polyanions contributed twice as much to the buildup of 8-K 30 /PLGA-L as 4-K 30 /PLGA-L.…”

“…2). From the perspective of UV absorbance at 217 nm for the 20-layer film, the fitting parameter ˇ or the amount of polyanion added per adsorption step, the 8-K 30 films grew faster than 4-K 30 .…”

Mannosylated lipopetides as model vaccines for targeting the mannose receptor

“…The design of a branched peptide vaccine has the advantage of presenting multiple copies of an epitope to the immune system in one single entity. Here, the lysine amino acid, containing both α and ε amino groups, provides branching points for the attachment of multiple peptide epitopes in one construct [248].…”