Date Thesis Awarded
5-2023
Access Type
Honors Thesis -- Access Restricted On-Campus Only
Degree Name
Bachelors of Science (BS)
Department
Chemistry
Advisor
Douglas Young
Committee Members
Lisa Landino
Shantá Hinton
Elizabeth Harbron
Abstract
Nature has evolved 20 amino acids that comprise all the proteins that compose living things. The limited lexicon of building blocks available to accomplish such a vast number of tasks is remarkable. My research aimed to augment protein chemistry by employing unnatural amino acids to modify proteins and introduce novel functionality. This was accomplished in three ways. First, we enabled modulation of Protein Methyltransferase function by incorporating a photocaged unnatural amino acid. A SAM510 Methyltransferase Assay revealed that the unnatural amino acid hindered methyltransferase activity in PRMT1 until irradiation with UV light, following which the photocaging group was removed, and protein activity was restored. Second, we achieved the dimerization of two proteins using a terminal alkyne-containing unnatural amino acid and a bioorthogonal Glaser-Hay reaction. We increased coupling efficiency by using a linker for this reaction. Finally, we synthesized a multivalent bioconjugate using a bromoalkyne unnatural amino acid and a reaction sequence including a bioorthogonal CuAAC followed by a Sonogashira. We demonstrated the use of an unnatural amino acid to confer spatiotemporal control over protein function. Additionally, we developed new pathways toward synthesizing bioconjugates, which have applications in targeted therapeutics, protein monitoring, and assays. Furthermore, a multivalent bioconjugate would expand the operational capacity of protein function by allowing the conjugation of multiple moieties, with each introducing a new function.
Recommended Citation
Burrow, Naya, "Modulation of Protein Function and Synthesis of Bioconjugates using Unnatural Amino Acids" (2023). Undergraduate Honors Theses. William & Mary. Paper 2042.
https://scholarworks.wm.edu/honorstheses/2042
