IMPIPS : The Immune Protection-Inducing Protein Structure concept in the search for steric-electron and topochemical principles for complete fully-protective chemically synthesised vaccine development

Determining immune protection-inducing protein structures (IMPIPS) involves defining the stereo-electron and topochemical characteristics which are essential in MHC-p-TCR complex formation. Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1∗structures. They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ∗-peptide binding regions (PBR). Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response. Immunological assays in Aotus monkeys involving IMPIPS mixtures led to promising results; taken together with the aforementioned physicochemical principles, noninterfering, long-lasting, protection-inducing, multi-epitope, multistage, minimal subunit-based chemically-synthesised peptides can be designed against diseases scourging humankind. © 2015 Patarroyo et al.

• Fecha de publicación: 2015
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/19030
• Acceso en línea: https://doi.org/10.1371/journal.pone.0123249; http://repository.urosario.edu.co/handle/10336/19030
• Palabra clave: Proteína de unión; epítopo; Antígeno Hla Dr; Hidrógeno; Vacuna contra la malaria; Nitrógeno; Oxígeno; Prolina; Cloruro de sodio; Péptido sintético; Vacuna recombinante; Animal Experiment; Modelo animal; Reacción de anticuerpo de antígeno; Aoto; Sitio de unión; Estudio controlado; Estructura de la droga; Electrón; Enlace de hidrógeno; Estructura proteica inductora de protección inmunitaria; Respuesta inmune; inmunoensayo; inmunogenicidad; Malaria; No humano; Virulencia del parásito; Síntesis de péptidos; Química Física; Plasmodium falciparum; Enlace proteico; Estructura de la proteína; Animal; Chemistry; Haplorhin; Conformación de proteínas; Biología; Synthetic; Vaccines; Proline; Synthetic Peptide; Sodium Chloride; Recombinant Vaccine; Animal Model; Animal Experiment; Antigen Antibody Reaction; Aotus; Binding Site; Controlled Study; Drug Structure; Electron; Hydrogen Bond; Immune Protection Inducing Protein; Structure; Immune Response; Immunoassay; Binding Protein; Epitope; Hla Dr Antigen; Hydrogen; Malaria Vaccine; Oxygen; Immunogenicity; Nonhuman; Parasite Virulence; Peptide Synthesis; Physical Chemistry; Plasmodium Falciparum; Protein Binding; Protein Structure; Chemistry; Protein Conformation; Haplorhini; Animals; Electrons; Nitrogen; Inmunología; Proteínas portadoras; Antígenos
• License: Abierto (Texto Completo)