Photocleavable approaches to reversible bioconjugation

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dc.contributor.advisorBall, Zachary Ten_US
dc.creatorMangubat-Medina, Alicia Een_US
dc.date.accessioned2019-12-20T14:46:13Zen_US
dc.date.available2021-05-01T05:01:09Zen_US
dc.date.created2020-05en_US
dc.date.issued2019-12-19en_US
dc.date.submittedMay 2020en_US
dc.date.updated2019-12-20T14:46:13Zen_US
dc.description.abstractThe folding of peptides and proteins depends on the structural conformation of the amide backbone. Historically, side-chain modifications that respond to external stimuli, such as light, were a convenient technique for controlling folding and activity. As our curiosity into complex biological systems matures, so must the techniques used to probe these systems. While thoroughly less reported than light-sensitive side-chain modifications (called photocages), light-responsive modifications to the amide backbone structure represents a direct and powerful alternative to impact structural conformation. Using a copper-mediated, histidine-directed peptide backbone modification with vinyl boronic acids, it was possible to insert a traceless photocage into the N-H bond of the amide backbone. Several obstacles required addressing in order to achieve a traceless backbone photocage: first, the bond formed required a previously unreported photocleavage between C(sp2) and N atoms. Second, the photocaging reagents must maintain a minimum level of solubility in an aqueous solution. Finally, for maximized general use in biological systems, light-induce uncaging would ideally occur using visible light and near infrared light. Here, the first peptide backbone photocaging reagents are described. These represent a new class of photocaging reagents capable of tracelessly uncaging peptides using ultraviolet, blue, and near-IR light; reversibly disrupting peptide folding; reversibly interrupting enzymatic recognition of a peptide substrate; and reversibly modifying a model protein. These results represent a jumping point to developing a vast array of backbone photocages, optimized for a wide variety of contexts.en_US
dc.embargo.terms2021-05-01en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationMangubat-Medina, Alicia E. "Photocleavable approaches to reversible bioconjugation." (2019) Diss., Rice University. <a href="https://hdl.handle.net/1911/107957">https://hdl.handle.net/1911/107957</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/107957en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectphotocageen_US
dc.subjectphotocleavageen_US
dc.subject2-photonen_US
dc.subjectpeptide backboneen_US
dc.subjectpeptide modificationen_US
dc.subjectprotein modificationen_US
dc.subjectcopper-mediateden_US
dc.subjecthistidine-directeden_US
dc.subjectsite-specificen_US
dc.subjectreversibleen_US
dc.subjectlight sensitiveen_US
dc.titlePhotocleavable approaches to reversible bioconjugationen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemistryen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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