Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective.

Título traducido de la contribución: Las regiones ligantes conservadas proporcionan la clave para el desarrollo de vacunas a base de péptidos: : Una perspectiva química.

Hernando Curtidor Castellanos, Cesar Reyes, Adriana Janneth Bermudez Quintero, Magnolia Vanegas Murcia, Yahson Varela, Manuel Elkin Patarroyo

Resultado de la investigación: Contribución a una revistaArtículo

4 Citas (Scopus)

Resumen

Los péptidos sintéticos se han convertido en herramientas inestimables de investigación biomédica y química medicinal para el estudio de los roles funcionales, es decir, la actividad ligante o proteolítica, la inmunogenicidad en proteínas de las regiones naturales y el desarrollo de agentes terapéuticos y vacunas. Los péptidos sintéticos pueden imitar sitios de proteínas; su estructura y función pueden ser fácilmente moduladas por el reemplazo de aminoácidos específicos. Tienen grandes ventajas, es decir, son baratos, fáciles de producir y químicamente estables, carecen de reacciones adversas infecciosas y secundarias y pueden inducir respuestas inmunitarias a través de epítopos de células T y B. Nuestro grupo ha demostrado anteriormente que el uso de péptidos sintéticos y la adopción de un enfoque funcional ha llevado a la identificación de regiones conservadas por Plasmodium falciparum que se unen a las células huéspedes. Se han tenido en cuenta las características fisicoquímicas, estructurales e inmunológicas de los "péptidos conservados de alta actividad de unión" (cHABP) para modificarlos y convertirlos en péptidos altamente inmunogénicos e inductores de protección (mHABP) en el modelo experimental del mono Aotus. Este artículo describe las características estereo-electrónicas y topoquímicas de la formación del complejo mayor del complejo de histocompatibilidad (MHC)-mHABP-T-cell receptor (TCR). Algunas de las mHABPs de este complejo que inducen una inmunidad protectora de larga duración han sido denominadas estructuras proteicas inductoras de protección inmunitaria (IMPIPS), que forman los componentes de la subunidad en vacunas químicamente sintetizadas. Este manuscrito resume este campo en particular y añade nuestros recientes hallazgos sobre las interacciones intramoleculares (H-bonds o π-interactions) que permiten una estructura IMPIPS adecuada, así como los residuos periféricos de flanqueo (PFR) para estabilizar la interacción MHCII-IMPIPS-TCR, con el objetivo de inducir una memoria inmunológica protectora y duradera.
Idioma originalInglés estadounidense
Número de artículo2199
Páginas (desde-hasta)1-31
Número de páginas31
PublicaciónMolecules
Volumen22
N.º12
DOI
EstadoPublicada - dic 22 2017

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Curtidor Castellanos, H., Reyes, C., Bermudez Quintero, A. J., Vanegas Murcia, M., Varela, Y., & Patarroyo, M. E. (2017). Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective. Molecules, 22(12), 1-31. [2199]. https://doi.org/10.3390/molecules22122199, https://doi.org/10.3390/molecules22122199
Curtidor Castellanos, Hernando ; Reyes, Cesar ; Bermudez Quintero, Adriana Janneth ; Vanegas Murcia, Magnolia ; Varela, Yahson ; Patarroyo, Manuel Elkin. / Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective. En: Molecules. 2017 ; Vol. 22, N.º 12. pp. 1-31.
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title = "Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development:: A Chemical Perspective.",
abstract = "Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions’ immunogenicity in proteins and developing therapeutic agents and vaccines. Synthetic peptides can mimic protein sites; their structure and function can be easily modulated by specific amino acid replacement. They have major advantages, i.e., they are cheap, easily-produced and chemically stable, lack infectious and secondary adverse reactions and can induce immune responses via T- and B-cell epitopes. Our group has previously shown that using synthetic peptides and adopting a functional approach has led to identifying Plasmodium falciparum conserved regions binding to host cells. Conserved high activity binding peptides’ (cHABPs) physicochemical, structural and immunological characteristics have been taken into account for properly modifying and converting them into highly immunogenic, protection-inducing peptides (mHABPs) in the experimental Aotus monkey model. This article describes stereo–electron and topochemical characteristics regarding major histocompatibility complex (MHC)-mHABP-T-cell receptor (TCR) complex formation. Some mHABPs in this complex inducing long-lasting, protective immunity have been named immune protection-inducing protein structures (IMPIPS), forming the subunit components in chemically synthesized vaccines. This manuscript summarizes this particular field and adds our recent findings concerning intramolecular interactions (H-bonds or π-interactions) enabling proper IMPIPS structure as well as the peripheral flanking residues (PFR) to stabilize the MHCII-IMPIPS-TCR interaction, aimed at inducing long-lasting, protective immunological memory.",
author = "{Curtidor Castellanos}, Hernando and Cesar Reyes and {Bermudez Quintero}, {Adriana Janneth} and {Vanegas Murcia}, Magnolia and Yahson Varela and Patarroyo, {Manuel Elkin}",
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Curtidor Castellanos, H, Reyes, C, Bermudez Quintero, AJ, Vanegas Murcia, M, Varela, Y & Patarroyo, ME 2017, 'Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective.', Molecules, vol. 22, n.º 12, 2199, pp. 1-31. https://doi.org/10.3390/molecules22122199, https://doi.org/10.3390/molecules22122199

Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective. / Curtidor Castellanos, Hernando; Reyes, Cesar; Bermudez Quintero, Adriana Janneth; Vanegas Murcia, Magnolia; Varela, Yahson; Patarroyo, Manuel Elkin.

En: Molecules, Vol. 22, N.º 12, 2199, 22.12.2017, p. 1-31.

Resultado de la investigación: Contribución a una revistaArtículo

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T1 - Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development:

T2 - A Chemical Perspective.

AU - Curtidor Castellanos, Hernando

AU - Reyes, Cesar

AU - Bermudez Quintero, Adriana Janneth

AU - Vanegas Murcia, Magnolia

AU - Varela, Yahson

AU - Patarroyo, Manuel Elkin

PY - 2017/12/22

Y1 - 2017/12/22

N2 - Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions’ immunogenicity in proteins and developing therapeutic agents and vaccines. Synthetic peptides can mimic protein sites; their structure and function can be easily modulated by specific amino acid replacement. They have major advantages, i.e., they are cheap, easily-produced and chemically stable, lack infectious and secondary adverse reactions and can induce immune responses via T- and B-cell epitopes. Our group has previously shown that using synthetic peptides and adopting a functional approach has led to identifying Plasmodium falciparum conserved regions binding to host cells. Conserved high activity binding peptides’ (cHABPs) physicochemical, structural and immunological characteristics have been taken into account for properly modifying and converting them into highly immunogenic, protection-inducing peptides (mHABPs) in the experimental Aotus monkey model. This article describes stereo–electron and topochemical characteristics regarding major histocompatibility complex (MHC)-mHABP-T-cell receptor (TCR) complex formation. Some mHABPs in this complex inducing long-lasting, protective immunity have been named immune protection-inducing protein structures (IMPIPS), forming the subunit components in chemically synthesized vaccines. This manuscript summarizes this particular field and adds our recent findings concerning intramolecular interactions (H-bonds or π-interactions) enabling proper IMPIPS structure as well as the peripheral flanking residues (PFR) to stabilize the MHCII-IMPIPS-TCR interaction, aimed at inducing long-lasting, protective immunological memory.

AB - Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions’ immunogenicity in proteins and developing therapeutic agents and vaccines. Synthetic peptides can mimic protein sites; their structure and function can be easily modulated by specific amino acid replacement. They have major advantages, i.e., they are cheap, easily-produced and chemically stable, lack infectious and secondary adverse reactions and can induce immune responses via T- and B-cell epitopes. Our group has previously shown that using synthetic peptides and adopting a functional approach has led to identifying Plasmodium falciparum conserved regions binding to host cells. Conserved high activity binding peptides’ (cHABPs) physicochemical, structural and immunological characteristics have been taken into account for properly modifying and converting them into highly immunogenic, protection-inducing peptides (mHABPs) in the experimental Aotus monkey model. This article describes stereo–electron and topochemical characteristics regarding major histocompatibility complex (MHC)-mHABP-T-cell receptor (TCR) complex formation. Some mHABPs in this complex inducing long-lasting, protective immunity have been named immune protection-inducing protein structures (IMPIPS), forming the subunit components in chemically synthesized vaccines. This manuscript summarizes this particular field and adds our recent findings concerning intramolecular interactions (H-bonds or π-interactions) enabling proper IMPIPS structure as well as the peripheral flanking residues (PFR) to stabilize the MHCII-IMPIPS-TCR interaction, aimed at inducing long-lasting, protective immunological memory.

U2 - 10.3390/molecules22122199

DO - 10.3390/molecules22122199

M3 - Article

C2 - 29231862

VL - 22

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JO - Molecules

JF - Molecules

SN - 1420-3049

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Curtidor Castellanos H, Reyes C, Bermudez Quintero AJ, Vanegas Murcia M, Varela Y, Patarroyo ME. Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective. Molecules. 2017 dic 22;22(12):1-31. 2199. https://doi.org/10.3390/molecules22122199, https://doi.org/10.3390/molecules22122199