Development of G9a-targeted BioPROTACs based on peptides and nanobodies

This project arose motivated by the high incidence that neoplastic pathologies have nowadays, and therefore by the need that our society has to find a solution against them. The main objective of this research was to identify specific peptides and nanobodies against G9a methyltransferase, whose r...

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Main Authors: Gómez-Vegas, L. (Lucía), Pineda-Lucena, A. (Antonio), Ibarra-García, V. (Vianca)
Format: info:eu-repo/semantics/bachelorThesis
Language:eng
Published: 2023
Subjects:
Online Access:https://hdl.handle.net/10171/66794
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author Gómez-Vegas, L. (Lucía)
Pineda-Lucena, A. (Antonio)
Ibarra-García, V. (Vianca)
author_facet Gómez-Vegas, L. (Lucía)
Pineda-Lucena, A. (Antonio)
Ibarra-García, V. (Vianca)
author_sort Gómez-Vegas, L. (Lucía)
collection DSpace
description This project arose motivated by the high incidence that neoplastic pathologies have nowadays, and therefore by the need that our society has to find a solution against them. The main objective of this research was to identify specific peptides and nanobodies against G9a methyltransferase, whose role in cancer is to introduce epigenetic modifications to silence tumor suppressor genes. The strategy followed focuses on degrading this enzyme through the Biological Proteolysis Targeting Chimera (BioPROTAC) system, made up of either the aforementioned peptides or nanobodies. A search for these specific molecules was carried out using phage display, to find the most specific candidates against the previously produced and purified G9a. Later, the binding affinity of the selected clones was evaluated, the BioPROTAC construct was designed, and immunocytochemistry (ICQ) was performed to check their cellular internalization. In short, it was possible to select 3 peptide clones and 16 nanobodies with a good affinity for G9a, in addition to designing a system capable of being introduced into the tumor cell. This represents a project of Targeted Protein Degradation (TPD) for drug discovery with its main objectives met. Furthermore, this study will facilitate future investigations aimed at confirming the efficacy of the system to degrade the enzyme, in order to conduct additional testing of its therapeutic effect.
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spelling oai:dadun.unav.edu:10171-667942023-07-10T05:17:34Z Development of G9a-targeted BioPROTACs based on peptides and nanobodies Gómez-Vegas, L. (Lucía) Pineda-Lucena, A. (Antonio) Ibarra-García, V. (Vianca) Materias Investigacion::Ciencias de la vida::Bioquímica Materias Investigacion::Ciencias de la vida Peptides Nanobodies This project arose motivated by the high incidence that neoplastic pathologies have nowadays, and therefore by the need that our society has to find a solution against them. The main objective of this research was to identify specific peptides and nanobodies against G9a methyltransferase, whose role in cancer is to introduce epigenetic modifications to silence tumor suppressor genes. The strategy followed focuses on degrading this enzyme through the Biological Proteolysis Targeting Chimera (BioPROTAC) system, made up of either the aforementioned peptides or nanobodies. A search for these specific molecules was carried out using phage display, to find the most specific candidates against the previously produced and purified G9a. Later, the binding affinity of the selected clones was evaluated, the BioPROTAC construct was designed, and immunocytochemistry (ICQ) was performed to check their cellular internalization. In short, it was possible to select 3 peptide clones and 16 nanobodies with a good affinity for G9a, in addition to designing a system capable of being introduced into the tumor cell. This represents a project of Targeted Protein Degradation (TPD) for drug discovery with its main objectives met. Furthermore, this study will facilitate future investigations aimed at confirming the efficacy of the system to degrade the enzyme, in order to conduct additional testing of its therapeutic effect. 2023-07-04T12:08:49Z 2023-07-04T12:08:49Z 2022 2023 info:eu-repo/semantics/bachelorThesis https://hdl.handle.net/10171/66794 eng info:eu-repo/semantics/openAccess application/pdf
spellingShingle Materias Investigacion::Ciencias de la vida::Bioquímica
Materias Investigacion::Ciencias de la vida
Peptides
Nanobodies
Gómez-Vegas, L. (Lucía)
Pineda-Lucena, A. (Antonio)
Ibarra-García, V. (Vianca)
Development of G9a-targeted BioPROTACs based on peptides and nanobodies
title Development of G9a-targeted BioPROTACs based on peptides and nanobodies
title_full Development of G9a-targeted BioPROTACs based on peptides and nanobodies
title_fullStr Development of G9a-targeted BioPROTACs based on peptides and nanobodies
title_full_unstemmed Development of G9a-targeted BioPROTACs based on peptides and nanobodies
title_short Development of G9a-targeted BioPROTACs based on peptides and nanobodies
title_sort development of g9a-targeted bioprotacs based on peptides and nanobodies
topic Materias Investigacion::Ciencias de la vida::Bioquímica
Materias Investigacion::Ciencias de la vida
Peptides
Nanobodies
url https://hdl.handle.net/10171/66794
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AT pinedalucenaaantonio developmentofg9atargetedbioprotacsbasedonpeptidesandnanobodies
AT ibarragarciavvianca developmentofg9atargetedbioprotacsbasedonpeptidesandnanobodies