Publicação
Development of novel biorthogonal tools for bioconjugation and controlled drug delivery
| datacite.subject.fos | Ciências Naturais::Ciências Químicas | pt_PT |
| dc.contributor.advisor | Afonso, Carlos Alberto Mateus | |
| dc.contributor.advisor | Trindade, Alexandre Fonseca Trindade | |
| dc.contributor.author | Ravasco, J. M. J. M | |
| dc.date.accessioned | 2023-06-28T11:06:16Z | |
| dc.date.available | 2025-07-01T00:30:36Z | |
| dc.date.issued | 2022-07 | |
| dc.date.submitted | 2021-11 | |
| dc.description.abstract | The term bioorthogonal chemistry encompasses any chemical reaction that can occur within living systems without interfering with their native biochemical processes. For that, these reactions such be high-yielding, fast and selective in addition biologically inert. Reactivity-wise these can be segregated into two major classes: 1) polar reactions and 2) cycloadditions. The search for better reactivity/stability balance in some bioorthogonal handles was a trigger for the fine-tuning of existing chemistries and exploration of new bioorthogonal mechanisms . Bioorthogonal chemistry became an essential asset to the fields of chemical biology, biomedical imaging, materials or surface science, with prominent application in metabolic engineering, proteomics, bioconjugation, drug-delivery and bioimaging. For such, metal-free 1,3-dipolar cycloaddition (1,3DC) and inverse-electron demand Diels-Alder (iEDDA) have been the gold-standard for their reactivity/stability profile. In this thesis, it will be firstly comprehensively discussed the evolution, the current limitations and strengths of the major bioorthogonal chemistries type as well as how their tunability have guided the development of mutually orthogonal bioorthogonal systems for drug-delivery and study of cellular mechanisms. Then, the development of data-driven multivariate models with robust predictive features for metal-free 1,3DC and iEDDA aiming to facilitate the design of novel reagents and experimental planning, without the need for expensive transition state calculations, will be presented. It will be discussed how these reagents interplay and how it can be used to design new scaffolds and pairs for multiplexed applications. Similar models will be applied to a class of modular bioimaging dyes (BASHY), providing a holistic view on key interactions governing probe stability, and allowing the de novo design of a stable hit dye. A BASHY-based caged bioorthogonal handle was also developed to confirm in cellulo the impact of BASHY stability in bioimaging. Finally, we present sustainable approaches to tackle biological systems, mainly based on the biomass-derived furanic platform. Additionally replacement of critical and rare materials with abundant materials is considered and exemplified by developing alternative routes bioorthogonal handle trans-cyclooctene. | pt_PT |
| dc.description.provenance | Submitted by Paula Guerreiro (passarinho@reitoria.ulisboa.pt) on 2023-05-16T13:58:52Z No. of bitstreams: 1 scnd740774_td_Joao_Ravasco.pdf: 29204855 bytes, checksum: 24fe213b658453ff29de59ac4ce1491d (MD5) | en |
| dc.description.provenance | Made available in DSpace on 2023-06-28T11:06:16Z (GMT). No. of bitstreams: 1 scnd740774_td_Joao_Ravasco.pdf: 29204855 bytes, checksum: 24fe213b658453ff29de59ac4ce1491d (MD5) Previous issue date: 2022-07 | en |
| dc.identifier.tid | 101554931 | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10451/58382 | |
| dc.language.iso | eng | pt_PT |
| dc.relation | Development of novel biorthogonal tools for bioconjugation and controlled drug delivery | |
| dc.subject | Química bioortogonal | pt_PT |
| dc.subject | Química biológica | pt_PT |
| dc.subject | Cicloadições | pt_PT |
| dc.subject | Análise preditiva multivariável | pt_PT |
| dc.subject | Química Sustentável | pt_PT |
| dc.subject | Bioorthogonal Chemistry | pt_PT |
| dc.subject | Biological Chemistry | pt_PT |
| dc.subject | Cycloadditions | pt_PT |
| dc.subject | Multivariate Predictive Analysis | pt_PT |
| dc.subject | Sustainable Chemistry | pt_PT |
| dc.title | Development of novel biorthogonal tools for bioconjugation and controlled drug delivery | pt_PT |
| dc.type | doctoral thesis | |
| dspace.entity.type | Publication | |
| oaire.awardNumber | SFRH/BD/120829/2016 | |
| oaire.awardTitle | Development of novel biorthogonal tools for bioconjugation and controlled drug delivery | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F120829%2F2016/PT | |
| person.familyName | Ravasco | |
| person.givenName | João Manuel Janeiro Martins | |
| person.identifier.ciencia-id | B31D-6FDA-1201 | |
| person.identifier.orcid | 0000-0001-7568-9613 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.contributor.authoremail | repositorio@reitoria.ulisboa.pt | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | doctoralThesis | pt_PT |
| relation.isAuthorOfPublication | ac35e971-56d6-464c-8a4b-027e21763cfd | |
| relation.isAuthorOfPublication.latestForDiscovery | ac35e971-56d6-464c-8a4b-027e21763cfd | |
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| thesis.degree.name | Tese de doutoramento, Farmácia (Química Farmacêutica e Terapêutica), Universidade de Lisboa, Faculdade de Farmácia, 2022 | pt_PT |