Synthesis of doxorubicin-protein conjugates via cobalt coordination chemistry: Conjugates of transferrin and immunoglobulin G

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dc.creatorCarvajal de Luna, Juan Jose
dc.creator.orcid0000-0002-3700-0771
dc.date.accessioned2022-01-06T22:36:39Z
dc.date.available2022-01-06T22:36:39Z
dc.date.created2021-12
dc.date.issued11/8/2021
dc.date.submitted21-Dec
dc.date.updated2022-01-06T22:36:40Z
dc.description.abstractProtein-drug conjugates are a rapidly expanding family of therapeutics that hold significant potential to ameliorate off-target toxic effects commonly observed in patients undergoing chemotherapy. chemotherapy. In this context, the protein acts as a nanoscale delivery vector that alters the biodistribution of the drug upon administration by restricting its unhindered distribution in vivo. This thesis explores the use of cobalt coordination chemistry in the synthesis of doxorubicin-protein conjugates. Previous work has shown that cobalt can be used to crosslink amine-containing molecules in a reversible reaction that only utilizes the lone pair of electrons on nitrogen to form a dative bond with cobalt. Doxorubicin was chosen for initial studies because it contains a primary amine that could be crosslinked with lysine residues on a protein to form a protein-drug conjugate. Conjugates of dox with albumin, transferrin, and immunoglobulin G were investigated to demonstrate the broad applicability of the method for bioconjugation reactions. Drug loading was investigated by HPLC, and the conjugates further characterized by dynamic light scattering, calorimetry, and cytotoxicity. Details of the effects of reaction conditions on synthesis of stable conjugates will be discussed.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/11274/13468
dc.language.isoen
dc.subjectProtein-drug conjugates
dc.subjectDoxorubicin-protein conjugates
dc.subjectCobalt coordination chemistry
dc.subjectConjugates of dox with albumin
dc.subjectTransferrin
dc.subjectImmunoglobulin G
dc.titleSynthesis of doxorubicin-protein conjugates via cobalt coordination chemistry: Conjugates of transferrin and immunoglobulin G
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentChemistry and Biochemistry
thesis.degree.disciplineChemistry
thesis.degree.grantorTexas Woman's University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science

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