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New strategies of bioconjugation for the synthesis of multifunctional bioconjugates

2023-07Tese de doutoramento Acesso restrito
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datacite.subject.fosCiências Médicas::Medicina Básicapt_PT
dc.contributor.advisorGóis, Pedro Miguel Pimenta
dc.contributor.advisorMendonça, Ricardo Filipe de Jesus Gonçalves
dc.contributor.authorDjaló, Mariama
dc.date.accessioned2024-06-03T09:04:33Z
dc.date.available2024-06-03T09:04:33Z
dc.date.issued2023-07
dc.date.submitted2023-04
dc.description.abstractThe recurrent discovery of new drug targets demanding innovative therapeutic agents further increases the need for new, highly selective, and active substances for future therapeutic applications. In this regard, chemical modification of peptides and proteins has emerged, and the significant progress accomplished in this field over the years allowed for the development of an extensive toolbox of bioconjugation technologies that enabled the creation of almost unlimited peptide and protein constructs with either naturally or synthetically modified residues. Recently, there has been a notable increase in interest in peptide-drug conjugates within the pharmaceutical industry. This is because peptides not only have relevant therapeutic applications but are also simple in design, relatively easy to synthesize and cost-effective. Moreover, researchers have been striving to develop multivalent reagents with the aim of creating bioconjugates with multiple functions with higher order of structural and functional complexity that aim to optimize biological studies and applications in vitro and in vivo. In this context, this thesis provides valuable insight into the construction of a new class of multivalent bioconjugation reagents for orthogonal functionalization of peptides at N terminal cysteines. These reagents, based on NHS-activated acrylates, present dual substitution and showed to site-selectively modify native peptides at the N-terminal cysteine, under biocompatible conditions in the micromolar range, without cross reacting with Lys, His, Ser, Thr, Tyr and in-chain Cys residues, resulting in stable bioconjugates. Furthermore, a Cys-bombesin peptide-drug conjugate was developed functionalized with a PEG chain, a coumarin probe and a cytotoxic drug, and was effectively used to label HeLa cells. Additionally, the pharmaceutical industry is also keen on investing in the development of effective drug delivery systems for the controlled administration of pre-existing drugs. In this thesis, we provide initial findings on the development of surface-modified particles in drug powder formulations.pt_PT
dc.description.provenanceSubmitted by Paula Guerreiro (passarinho@reitoria.ulisboa.pt) on 2024-05-24T14:01:04Z No. of bitstreams: 1 scnd990026354741668_td_Mariama_Djaló.pdf: 21606483 bytes, checksum: 3043dbd980b9f87a50c53852aa9ca055 (MD5)en
dc.description.provenanceMade available in DSpace on 2024-06-03T09:04:33Z (GMT). No. of bitstreams: 1 scnd990026354741668_td_Mariama_Djaló.pdf: 21606483 bytes, checksum: 3043dbd980b9f87a50c53852aa9ca055 (MD5) Previous issue date: 2023-07en
dc.identifier.tid101636652pt_PT
dc.identifier.urihttp://hdl.handle.net/10451/64954
dc.language.isoengpt_PT
dc.subjectBioconjugaçãopt_PT
dc.subjectseletividade posicionalpt_PT
dc.subjectreagentes ortogonais multifuncionaispt_PT
dc.subjectconjugados fármaco-péptidopt_PT
dc.subjectsistemas avançados de entrega de fármacopt_PT
dc.subjectBioconjugationpt_PT
dc.subjectsite-selectivitypt_PT
dc.subjectmultivalent orthogonal reagentspt_PT
dc.subjectpeptide-drug conjugatept_PT
dc.subjectadvanced drug delivery systemspt_PT
dc.titleNew strategies of bioconjugation for the synthesis of multifunctional bioconjugatespt_PT
dc.typedoctoral thesis
dspace.entity.typePublication
oaire.awardNumberPD/BD/143155/2019
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F143155%2F2019/PT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.contributor.authoremailrepositorio@reitoria.ulisboa.pt
rcaap.rightsrestrictedAccesspt_PT
rcaap.typedoctoralThesispt_PT
relation.isProjectOfPublication00c402df-89e0-4aa9-af62-b108c5612161
relation.isProjectOfPublication.latestForDiscovery00c402df-89e0-4aa9-af62-b108c5612161
thesis.degree.nameTese de doutoramento, Farmácia (Química Farmacêutica e Terapêutica), Universidade de Lisboa, Faculdade de Farmácia, 2023pt_PT

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