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

Manuel Elkin Patarroyo, Adriana Bermúdez, Martha Patricia Alba, Magnolia Vanegas, Armando Moreno-Vranich, Luis Antonio Poloche, Manuel Alfonso Patarroyo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

24 Citas (Scopus)

Resumen

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.

Idioma originalInglés estadounidense
Número de artículoe0123249
PublicaciónPLOS ONE
Volumen10
N.º4
DOI
EstadoPublicada - abr. 16 2015

Áreas temáticas de ASJC Scopus

  • Bioquímica, Genética y Biología Molecular General
  • Ciencias Agrícolas y Biológicas General
  • General

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