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dc.contributor.advisor Ball, Zachary T
dc.creatorMangubat-Medina, Alicia E
dc.date.accessioned 2019-12-20T14:46:13Z
dc.date.created 2020-05
dc.date.issued 2019-12-19
dc.date.submitted May 2020
dc.identifier.citation Mangubat-Medina, Alicia E. "Photocleavable approaches to reversible bioconjugation." (2019) Diss., Rice University. https://hdl.handle.net/1911/107957.
dc.identifier.urihttps://hdl.handle.net/1911/107957
dc.description.abstract The 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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectphotocage
photocleavage
2-photon
peptide backbone
peptide modification
protein modification
copper-mediated
histidine-directed
site-specific
reversible
light sensitive
dc.title Photocleavable approaches to reversible bioconjugation
dc.type Thesis
dc.date.updated 2019-12-20T14:46:13Z
dc.type.material Text
thesis.degree.department Chemistry
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy
dc.embargo.terms 2021-05-01
dc.embargo.lift 2021-05-01


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