Development of designed site-directed pseudopeptide-peptido-mimetic immunogens as novel minimal subunit-vaccine candidates for malaria.
Synthetic vaccines constitute the most promising tools for controlling and preventing infectious diseases. When synthetic immunogens are designed from the pathogen native sequences, these are normally poorly immunogenic and do not induce protection, as demonstrated in our research. After attempting many synthetic strategies for improving the immunogenicity properties of these sequences, the approach consisting of identifying high binding motifs present in those, and then performing specific changes on amino-acids belonging to such motifs, has proven to be a workable strategy. In addition, other strategies consisting of chemically introducing non-natural constraints to the backbone topology of the molecule and modifying the α-carbon asymmetry are becoming valuable tools to be considered in this pursuit. Non-natural structural constraints to the peptide backbone can be achieved by introducing peptide bond isosters such as reduced amides, partially retro or retro-inverso modifications or even including urea motifs. The second can be obtained by strategically replacing L-amino-acids with their enantiomeric forms for obtaining both structurally site-directed designed immunogens as potential vaccine candidates and their Ig structural molecular images, both having immuno-therapeutic effects for preventing and controlling malaria.
Fundación Instituto de Inmunología de Colombia (FIDIC), Universidad del Rosario and Universidad Nacional de Colombia, Bogotá DC, Colombia. jm_lozano@fidic.org.co
José Manuel
JM
Lozano
Liliana P
LP
Lesmes
Luisa F
LF
Carreño
Gina M
GM
Gallego
Manuel Elkin
ME
Patarroyo
D000818:Animals; D000882:Haplorhini; D006801:Humans; D017780:Malaria Vaccines / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D022223:Vaccines, Subunit / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology
D017780:Malaria Vaccines; D057786:Peptidomimetics; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic