title: Gauche(+) side-chain orientation as a key factor in the search for an immunogenic peptide mixture leading to a complete fully protective vaccine.
abstract: Topological and stereo-electron characteristics are essential in major histocompability class II-peptide-T-cell receptor (MHC-p-TCR) complex formation for inducing an appropriate immune response. Modified high activity binding peptides (mHABPs) were synthesised for complete full protection antimalarial vaccine development producing a large panel of individually fully protection-inducing protein structures (FPIPS) and very high long-lasting antibody-inducing (VHLLAI) mHABPs. Most of those which did not interfere, compete, inhibit or suppress their individual VHLLAI or FPIPS activity contained or displayed a polyproline II-like (PPIIL) structure when mixed. Here we show that amino acid side-chains located in peptide binding region (PBR) positions p3 and p7 displayed specific electron charges and side-chain gauche(+) orientation for interacting with the TCR. Based on the above, and previously described physicochemical principles, non-interfering, long-lasting, full protection-inducing, multi-epitope, multistage, minimal subunit-based chemically synthesised mHABP mixtures can be designed for developing vaccines against diseases scourging humankind, malaria being one of them.
authors.affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50, # 26-20, Bogotá, Colombia; Universidad del Rosario, Calle 14, # 6-25, Bogotá, Colombia.
authors.forename: Adriana
authors.initials: A
authors.lastname: Bermúdez
authors.affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50, # 26-20, Bogotá, Colombia.
authors.forename: Dayana
authors.initials: D
authors.lastname: Calderon
authors.affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50, # 26-20, Bogotá, Colombia.
authors.forename: Armando
authors.initials: A
authors.lastname: Moreno-Vranich
authors.affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50, # 26-20, Bogotá, Colombia.
authors.forename: Hannia
authors.initials: H
authors.lastname: Almonacid
authors.affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50, # 26-20, Bogotá, Colombia; Universidad del Rosario, Calle 14, # 6-25, Bogotá, Colombia.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Patarroyo
authors.affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50, # 26-20, Bogotá, Colombia.
authors.forename: Andrés
authors.initials: A
authors.lastname: Poloche
authors.affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50, # 26-20, Bogotá, Colombia; Universidad Nacional de Colombia, Carrera 45, # 26-85, Bogotá, Colombia. Electronic address: mepatarr@gmail.com.
authors.forename: Manuel E
authors.initials: ME
authors.lastname: Patarroyo
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000917:Antibody Formation; D001029:Aotus trivirgatus; D001665:Binding Sites; D059806:HLA-DR beta-Chains / Q000276:immunology; D017780:Malaria Vaccines / Q000737:chemistry*; D016778:Malaria, Falciparum / Q000517:prevention & control; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology*; D011487:Protein Conformation
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D059806:HLA-DR beta-Chains; D017780:Malaria Vaccines; D009842:Oligopeptides
keywords: Antimalarial vaccine; Gauche(+); Peptide mixtures; Protective immunity; χ(1) angle