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http://dx.doi.org/10.25673/114502
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DC Field | Value | Language |
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dc.contributor.referee | Wessjohann, Ludger | - |
dc.contributor.referee | Rennert, Robert | - |
dc.contributor.referee | Rivera, Daniel Garcia | - |
dc.contributor.referee | Kaluđerović, Goran | - |
dc.contributor.author | Llanes Martinez, Dayma | - |
dc.date.accessioned | 2024-02-12T13:17:22Z | - |
dc.date.available | 2024-02-12T13:17:22Z | - |
dc.date.issued | 2023 | - |
dc.identifier.uri | https://opendata.uni-halle.de//handle/1981185920/116459 | - |
dc.identifier.uri | http://dx.doi.org/10.25673/114502 | - |
dc.description.abstract | This thesis focuses on the development of solid-phase synthesis and biological study of novel analogs of tubulysins called “tubugis”. The present document describes in the first chapter the state-of-the-art of chemical and biological features of tubulysins and their synthetic analogs. In the second chapter, a solid-phase approach including an on-resin Ugi 4-component reaction was developed for the construction of tubugis. The solid-phase and multicomponent methods developed before were used for the introduction of diverse functionalities at the N-tertiary amide, which is described in the third chapter. The fourth chapter describes the synthesis of novel Peptide drug conjugates based on the conjugation of the specially functionalized tubugis to bombesin, a targeting peptide with applications in cancer imaging and treatment. Using disulfide-based linkages, chemistry with proven stability, and selective cleavage properties, three different Bombesin-tubugi conjugates were obtained. | eng |
dc.description.abstract | Diese Dissertation konzentriert sich auf die Entwicklung einer Festphasensynthese neuartiger Tubulysin-Analoga. Das Design und die biologische Charakterisierung dieser sog. „Tubugis“ behandelt. Das erste Kapitel beschreibt den Stand der Technik und die chemisch/ biologischen Eigenschaften von Tubulysinen, sowie ihrer synthetischen Analoga. Im zweiten Kapitel wird die entwickelte Synthese mittels der Ugi-4-Komponenten-Reaktion von Tubugis behandelt. Im dritten Kapitel werden die Verwendung zur Einführung diverser unktionalitäten am N-tertiären Amidrest beschrieben. Das vierte Kapitel beschreibt die Synthese neuartiger Peptid-Wirkstoff Konjugate basierend auf der Konjugation des neu funktionalisierten Tubugis an Bombesin ein zielgerichtetes Peptid mit Anwendungen in Krebsbildgebung und behandlung. Es konnten drei verschiedene Bombesin-Tubugi-Konjugate mittels Disulfidbindungen, einer Chemie mit nachgewiesener Stabilität und selektiven Spaltungseigenschaften, hergestellt werden. | ger |
dc.format.extent | 1 Online-Ressource (117, XXXVIII Seiten) | - |
dc.language.iso | eng | - |
dc.rights.uri | https://creativecommons.org/licenses/by-sa/4.0/ | - |
dc.subject.ddc | 540 | - |
dc.title | Synthesis, conjugation, and biological evaluation of new N-functionalized tubugis | eng |
dcterms.dateAccepted | 2023-11-21 | - |
dcterms.type | Hochschulschrift | - |
dc.type | PhDThesis | - |
dc.identifier.urn | urn:nbn:de:gbv:3:4-1981185920-1164594 | - |
local.versionType | publishedVersion | - |
local.publisher.universityOrInstitution | Martin-Luther-Universität Halle-Wittenberg | - |
local.subject.keywords | Tubulysin, Tubugi, Ugi-4-component reaction, Peptide drug conjugates, Ugi-4-Komponenten-Reaktion, Peptid-Wirkstoff Konjugate | - |
local.openaccess | true | - |
dc.identifier.ppn | 1880534983 | - |
cbs.publication.displayform | Halle, 2023 | - |
local.publication.country | XA-DE | - |
cbs.sru.importDate | 2024-02-12T13:16:36Z | - |
local.accessrights.dnb | free | - |
Appears in Collections: | Interne-Einreichungen |
Files in This Item:
File | Description | Size | Format | |
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Dissertation_MLU_2024_LlanesMartinezDayma.pdf | 8.5 MB | Adobe PDF | ![]() View/Open |