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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov Nov 2023

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …


Mechanism-Driven Approaches And Novel Constructs For High Purity Rna Synthesis, Kithmie Malagodapathiranage Apr 2023

Mechanism-Driven Approaches And Novel Constructs For High Purity Rna Synthesis, Kithmie Malagodapathiranage

Doctoral Dissertations

RNA is poised to revolutionize medicine. By simply changing the sequence, one therapeutic can be converted into a wholly new one, with little or no change in manufacturing and formulation. While a single mRNA vaccine produced at massive scale can treat billions, the re-codability of RNA will also enable the widespread growth of personalized medicines. T7 RNA polymerase is highly efficient at the synthesis of therapeutic RNA, but is known to produce unintended RNA impurities during synthesis. These products arise from the encoded RNA rebinding the enzyme such that its 3’ end serves as a primer for extension. This leads …