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dc.contributor.advisorJewett, John C.en
dc.contributor.authorMehari, Bereketab Tesfayesus
dc.creatorMehari, Bereketab Tesfayesusen
dc.date.accessioned2018-02-19T16:08:49Z
dc.date.available2018-02-19T16:08:49Z
dc.date.issued2018
dc.identifier.urihttp://hdl.handle.net/10150/626654
dc.description.abstractBioconjugation strategies for chemical modification of biomolecules play an important role in gaining greater understanding of biological processes. A number of chemical reactions have been developed for labeling biomolecules in biologically relevant conditions. In an effort to expand the chemical tools available for biological studies, the Jewett group is working towards developing new and improving current bioconjugation strategies to address questions in chemical biology. The traceless Bertozzi-Staudinger reaction is one of the most selective bioconjugation reactions. However, its utility is limited due to poor solubility in aqueous conditions and challenges in the synthesis of functionalized variations of the reagent. A modular one-pot synthetic strategy has been developed. It was also demonstrated that this method can be used to introduce aldehyde and azide functionalities as chemical handles for modification of these reagents. In addition, the design and synthesis of a traceless Bertozzi-Staudinger reagent that has been functionalized with a triazabutadiene probe is described. The orthogonal nature of the traceless Bertozzi-Staudinger and triazabutadiene moieties was established. The utility of the bifunctionalized reagent as a tool for attaching a cargo onto the traceless Bertozzi-Staudinger reagent by utilizing the reactivity of the triazabutadiene moiety and vice versa was demonstrated using a model compound. It was also shown that the reagents that have been modified using this strategy retained their chemical reactivity. In conclusion, this work describes the design and synthesis of bioconjugation reagents that can expand the toolbox of reagents available for the study of biological process.
dc.language.isoen_USen
dc.publisherThe University of Arizona.en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en
dc.titleDesign and Synthesis of Modular Reagents for Chemical Biologyen_US
dc.typetexten
dc.typeElectronic Dissertationen
thesis.degree.grantorUniversity of Arizonaen
thesis.degree.leveldoctoralen
dc.contributor.committeememberJewett, John C.en
dc.contributor.committeememberGlass, Richard S.en
dc.contributor.committeememberHruby, Victor J.en
dc.contributor.committeememberMash, Eugene A.en
thesis.degree.disciplineGraduate Collegeen
thesis.degree.disciplineChemistryen
thesis.degree.namePh.D.en
refterms.dateFOA2018-06-16T09:03:39Z
html.description.abstractBioconjugation strategies for chemical modification of biomolecules play an important role in gaining greater understanding of biological processes. A number of chemical reactions have been developed for labeling biomolecules in biologically relevant conditions. In an effort to expand the chemical tools available for biological studies, the Jewett group is working towards developing new and improving current bioconjugation strategies to address questions in chemical biology. The traceless Bertozzi-Staudinger reaction is one of the most selective bioconjugation reactions. However, its utility is limited due to poor solubility in aqueous conditions and challenges in the synthesis of functionalized variations of the reagent. A modular one-pot synthetic strategy has been developed. It was also demonstrated that this method can be used to introduce aldehyde and azide functionalities as chemical handles for modification of these reagents. In addition, the design and synthesis of a traceless Bertozzi-Staudinger reagent that has been functionalized with a triazabutadiene probe is described. The orthogonal nature of the traceless Bertozzi-Staudinger and triazabutadiene moieties was established. The utility of the bifunctionalized reagent as a tool for attaching a cargo onto the traceless Bertozzi-Staudinger reagent by utilizing the reactivity of the triazabutadiene moiety and vice versa was demonstrated using a model compound. It was also shown that the reagents that have been modified using this strategy retained their chemical reactivity. In conclusion, this work describes the design and synthesis of bioconjugation reagents that can expand the toolbox of reagents available for the study of biological process.


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