Graduation Year
2017
Date of Submission
12-2016
Document Type
Open Access Senior Thesis
Degree Name
Bachelor of Arts
Department
Chemistry
Reader 1
Aaron Leconte
Reader 2
Arlie Rinaldi
Terms of Use & License Information
Rights Information
© 2016 Nedim Filipovic
Abstract
In vitro protein selection has had major impacts in the field of protein engineering. Traditional screens assay individual proteins for specific function. Selection, however, analyzes a pool of mutants and yields the best variants. Phage display, a successful selection technique, also provides a reliable link between variant phenotype and genotype. It can also be coupled with high throughput sequencing to map protein mutations; potentially highlighting vital mutations in variants. We propose to apply this technique to cancer therapy. RAF, a serine/threonine kinase, is critical for cell regulation in mammals. RAF can be activated by oncogenic RAS, found in over 30% of cancers, to drive cancer proliferation. Rigosertib, a benzyl styryl sulfone in phase III clinical trials for myelodysplastic syndrome (MDS), is an inhibitor of the RAS binding domain (RBD) in RAF. Phage display can be used to select RAF mutants for RAS binding affinity, in the presence of Rigosertib. High-throughput sequencing of these variants can provide a means of anticipating, and mapping resistance to this anti-cancer drug.
Recommended Citation
Filipovic, Nedim, "Phage display to identify functional resistance mutations to Rigosertib" (2017). CMC Senior Theses. 1475.
https://scholarship.claremont.edu/cmc_theses/1475
Included in
Biochemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Other Chemistry Commons
