Determinación y caracterización de las regiones de unión de PfRON4 a eritrocitos y hepatocitos humanos

ilustraciones

Autores:
Pulido Quevedo, Fredy Alexander
Tipo de recurso:
Fecha de publicación:
2023
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/83010
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/83010
https://repositorio.unal.edu.co/
Palabra clave:
570 - Biología::572 - Bioquímica
610 - Medicina y salud::616 - Enfermedades
Vacunas
Parásitos
Vaccines
Parasites
malaria
proteína del cuello de las roptrias 4
péptidos sintéticos.
Plasmodium falciparum
rhoptry neck protein 4
synthetic peptides
Rights
openAccess
License
Atribución-NoComercial-SinDerivadas 4.0 Internacional
id UNACIONAL2_f6f3d2c494293fb38f47787b3f27b6af
oai_identifier_str oai:repositorio.unal.edu.co:unal/83010
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Determinación y caracterización de las regiones de unión de PfRON4 a eritrocitos y hepatocitos humanos
dc.title.translated.eng.fl_str_mv Determination and characterization PfRON4's binding regions to human erythrocytes and hepatocytes
title Determinación y caracterización de las regiones de unión de PfRON4 a eritrocitos y hepatocitos humanos
spellingShingle Determinación y caracterización de las regiones de unión de PfRON4 a eritrocitos y hepatocitos humanos
570 - Biología::572 - Bioquímica
610 - Medicina y salud::616 - Enfermedades
Vacunas
Parásitos
Vaccines
Parasites
malaria
proteína del cuello de las roptrias 4
péptidos sintéticos.
Plasmodium falciparum
rhoptry neck protein 4
synthetic peptides
title_short Determinación y caracterización de las regiones de unión de PfRON4 a eritrocitos y hepatocitos humanos
title_full Determinación y caracterización de las regiones de unión de PfRON4 a eritrocitos y hepatocitos humanos
title_fullStr Determinación y caracterización de las regiones de unión de PfRON4 a eritrocitos y hepatocitos humanos
title_full_unstemmed Determinación y caracterización de las regiones de unión de PfRON4 a eritrocitos y hepatocitos humanos
title_sort Determinación y caracterización de las regiones de unión de PfRON4 a eritrocitos y hepatocitos humanos
dc.creator.fl_str_mv Pulido Quevedo, Fredy Alexander
dc.contributor.advisor.none.fl_str_mv Arévalo Pinzón, Gabriela
Patarroyo Gutiérrez, Manuel Alfonso
dc.contributor.author.none.fl_str_mv Pulido Quevedo, Fredy Alexander
dc.contributor.researchgroup.spa.fl_str_mv Receptor-Ligando
dc.contributor.orcid.spa.fl_str_mv https://orcid.org/0000-0003-4395-3672
dc.subject.ddc.spa.fl_str_mv 570 - Biología::572 - Bioquímica
610 - Medicina y salud::616 - Enfermedades
topic 570 - Biología::572 - Bioquímica
610 - Medicina y salud::616 - Enfermedades
Vacunas
Parásitos
Vaccines
Parasites
malaria
proteína del cuello de las roptrias 4
péptidos sintéticos.
Plasmodium falciparum
rhoptry neck protein 4
synthetic peptides
dc.subject.lemb.spa.fl_str_mv Vacunas
Parásitos
dc.subject.lemb.eng.fl_str_mv Vaccines
Parasites
dc.subject.proposal.spa.fl_str_mv malaria
proteína del cuello de las roptrias 4
péptidos sintéticos.
dc.subject.proposal.none.fl_str_mv Plasmodium falciparum
dc.subject.proposal.eng.fl_str_mv rhoptry neck protein 4
synthetic peptides
description ilustraciones
publishDate 2023
dc.date.accessioned.none.fl_str_mv 2023-01-18T16:27:59Z
dc.date.available.none.fl_str_mv 2023-01-18T16:27:59Z
dc.date.issued.none.fl_str_mv 2023-01-17
dc.type.spa.fl_str_mv Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TM
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/83010
dc.identifier.instname.spa.fl_str_mv Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv https://repositorio.unal.edu.co/
url https://repositorio.unal.edu.co/handle/unal/83010
https://repositorio.unal.edu.co/
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
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107. Koussis K, Withers‐Martinez C, Yeoh S, Child M, Hackett F, Knuepfer E, et al. A multifunctional serine protease primes the malaria parasite for red blood cell invasion. 2009;28(6):725-35.
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dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.license.spa.fl_str_mv Atribución-NoComercial-SinDerivadas 4.0 Internacional
dc.rights.uri.spa.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv Atribución-NoComercial-SinDerivadas 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv xv, 90 páginas
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dc.publisher.spa.fl_str_mv Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv Bogotá - Medicina - Maestría en Bioquímica
dc.publisher.faculty.spa.fl_str_mv Facultad de Medicina
dc.publisher.place.spa.fl_str_mv Bogotá, Colombia
dc.publisher.branch.spa.fl_str_mv Universidad Nacional de Colombia - Sede Bogotá
institution Universidad Nacional de Colombia
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spelling Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Arévalo Pinzón, Gabriela3dd83e7b546fe22342d6cc31cc2cbc79Patarroyo Gutiérrez, Manuel Alfonso30322a85ae0ad9c1368bae791386bffePulido Quevedo, Fredy Alexander03f9a2f410f261c132b10d80e6adb61fReceptor-Ligandohttps://orcid.org/0000-0003-4395-36722023-01-18T16:27:59Z2023-01-18T16:27:59Z2023-01-17https://repositorio.unal.edu.co/handle/unal/83010Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustracionesPlasmodium falciparum durante su ciclo de vida, expresa una amplia gama de proteínas entre las que se destaca la proteína del cuello de las roptrias 4 (PfRON4). Este es un candidato promisorio a vacuna, ya que se expresa tanto en merozoítos como esporozoítos, participa durante la formación del enlace fuerte con la célula hospedera a través del complejo RONs/AMA1 y es refractario a deleción genética. Pese a ello, aún no se conocen las regiones clave de este antígeno que interactúan con las células hospederas, siendo esta información de gran utilidad para combatir la enfermedad causada por este parásito. Por tal motivo, en este trabajo de investigación se sintetizaron 32 péptidos derivados de la región conservada de PfRON4 y se llevaron a cabo ensayos de interacción receptor-ligando para determinar la capacidad de unión de cada péptido a células hospederas, así como determinar la naturaleza del receptor y habilidad de éstos para inhibir la invasión del parásito en cultivo continuo in vitro con la cepa FCB2. Se identificaron cinco HABPs (High Activity Binding Peptides) denominados 42477, 42479, 42480, 42505 y 42513, los cuales se unieron con alta afinidad y especificidad a receptores de tipo proteico sobre la membrana de los eritrocitos. Por su parte, los péptidos 42477 y 42480 se unieron a la membrana de las células HepG2 con constantes de disociación en el rango sub-micromolar, siendo esta interacción dependiente de receptores tipo heparina y/o sulfato de condroitina. Los ensayos de inhibición de la invasión mostraron que los HABPs de PfRON4 fueron capaces de bloquear la entrada de los merozoítos a los eritrocitos hasta en un 50%. En conclusión, se encontró que las regiones de PfRON4 800-819 (42477) y 860-879 (42480) interactúan específicamente con las células hospederas y esto soporta su inclusión en el desarrollo de una vacuna multi-antígeno, multi-estadio basada en subunidades contra P. falciparum (Texto tomado de la fuente)Plasmodium falciparum expresses a wide range of proteins during its lifecycle, among which one the most important is rhoptry neck protein 4 (PfRON4); it is a promising vaccine candidate since it is expressed in merozoites and sporozoites, participates in a strong bond formation with host cells via the RONs/AMA-1 complex and is refractory to genetic deletion. Despite this, PfRON4’s key regions interacting with host cells remain unknown; such information would be extremely useful for combating P. falciparum-related malaria. For this reason, in this research work, thirty-two PfRON4 conserved region-derived synthetic peptides were chemically synthesized, and receptor-ligand interaction/binding assays were carried out for determining the binding capacity of each peptide to host cells, the nature of their receptors and their ability to inhibit in vitro parasite invasion with the FCB2 strain. Five HABPS (High Activity Binding Peptides) named 42477, 42479, 42480, 42505 and 42513 were identified, which bound with high affinity and specificity to protein-like receptors on the erythrocyte membrane. Peptides 42477 and 42480 bound to HepG2 cells’ membrane, both of them having submicromolar range kD, the interaction being dependent on heparin and/or chondroitin sulphate proteoglycan receptors. Invasion inhibition assays showed that PfRON4 HABPs were able to block merozoite entry into erythrocytes by up to 50%. In conclusion, PfRON4 regions 800-819 (42477) and 860-879 (42480) were found to specifically interact with host cells, which supports their inclusion in the development of a subunit-based, multi-antigen, multistage anti-malarial vaccine against P. falciparumMaestríaMagister en BioquímicaBioquímica y Biología Molecularxv, 90 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Maestría en BioquímicaFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá570 - Biología::572 - Bioquímica610 - Medicina y salud::616 - EnfermedadesVacunasParásitosVaccinesParasitesmalariaproteína del cuello de las roptrias 4péptidos sintéticos.Plasmodium falciparumrhoptry neck protein 4synthetic peptidesDeterminación y caracterización de las regiones de unión de PfRON4 a eritrocitos y hepatocitos humanosDetermination and characterization PfRON4's binding regions to human erythrocytes and hepatocytesTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TM1. 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Bliss' and Loewe's additive and synergistic effects in Plasmodium falciparum growth inhibition by AMA1-RON2L, RH5, RIPR and CyRPA antibody combinations. 2020;10(1):1-12.InvestigadoresLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/83010/3/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD53ORIGINAL1026288216.2022.pdf1026288216.2022.pdfTesis de Maestría en Bioquímicaapplication/pdf3713705https://repositorio.unal.edu.co/bitstream/unal/83010/4/1026288216.2022.pdf2e24ae94dbcdf8587cb25fb42e69e49fMD54THUMBNAIL1026288216.2022.pdf.jpg1026288216.2022.pdf.jpgGenerated Thumbnailimage/jpeg4948https://repositorio.unal.edu.co/bitstream/unal/83010/5/1026288216.2022.pdf.jpg218a3ed687237e4a9e81daa4664da5fbMD55unal/83010oai:repositorio.unal.edu.co:unal/830102024-08-15 23:14:21.599Repositorio Institucional Universidad Nacional de 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