Towards a Poly-Functional Synthetic-Antimalarial Vaccine: Incorporating Non-Natural Elements into Artificially-Made Peptides for Mimicking Functional Pathogen Ligand Structures Representing New Site-Directed Vaccine Components
Jose Manuel Lozano,
Manuel Elkin Patarroyo.
The molecular basis for obtaining novel anti-malarial vaccine candidates depends on a considered selection of
antigenic peptides, mainly derived from Plasmodium antigens’ non-polymorphic regions. Since such targeted-molecules
are poorly immunogenic when tested as vaccine components, they usually have to be modified to overcome their
immunological phenotype. Transition state theory, explaining how peptidases catalyse a given peptide bond breakage,
thus led to reduced amide pseudopeptides being proposed as possible mimetics for a transition-state. Stabilising such
high-energy molecular stages could become a strategy for inducing antibodies potentially harbouring catalytic properties.
Hence, isostere-bond peptido-mimetics represented a rational choice as potential abzyme-inducers and site-directed
designed reduced amide pseudopeptides for obtaining peptide-analogues from selected malarial high-binding motifs. This
novel family of vaccine candidates has proved to be an efficient functional antibody-inducer, the latter acting as efficient
blockers of Plasmodium infection of human and mouse RBCs.
Keywords: Antimalarial vaccine, catalytic antibody, passive immunisation, peptide-bond isostere, peptido-mimetic,
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