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Full text release has been delayed at the author's request until August 04, 2029

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Development of peptide-based pan-Ras protein degraders

Sarkar, Amar
http://rave.ohiolink.edu/etdc/view?acc_num=osu1714964682314997

Abstract Details

2024, Doctor of Philosophy, Ohio State University, Chemistry.
In recent years, proteolysis-targeting chimera (PROTAC) technology has induced a paradigm shift in drug discovery efforts, especially in targeting difficult oncology targets. However, more than 80 percent of the human proteome is beyond the reach of small molecules. Consequently, such targets remain elusive to small-molecule PROTACs as well. Peptides, on the other hand, have superior potential when it comes to targeting proteins traditionally known as ‘undruggable’ due to their large surface area, swift and easy identification, ease of modifications, biocompatibility, and low toxicities. However, exploration of peptide based PROTACs is highly limited. One of the major bottlenecks of peptide based PROTACs is the issue of cell permeability. This study presents a pivotal investigation delineating the strategic conversion of a cell-permeable peptide binder into a potent PROTAC entity. This study successfully attempts to develop degraders against pan-Ras for the first time. Ras is a formidable and highly sought-after target in oncology, and our study has validated the enormous potential of peptide PROTACs for targeting such a difficult protein. Similar attempts to convert cell-permeable peptide binders into degraders would significantly expand the chemical space of PROTACs and peptide therapeutics.
Dehua Pei (Advisor)
Dmitri Kudryashov (Committee Member)
Dennis Bong (Committee Member)
156 p.
Chemistry
PROTACs, Peptide Therapeutics, Ras Therapeutics, Ras Inhibitors, Peptide-based PROTACs

Recommended Citations

Citations

  • Sarkar, A. (2024). Development of peptide-based pan-Ras protein degraders [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1714964682314997

    APA Style (7th edition)

  • Sarkar, Amar. Development of peptide-based pan-Ras protein degraders. 2024. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1714964682314997.

    MLA Style (8th edition)

  • Sarkar, Amar. "Development of peptide-based pan-Ras protein degraders." Doctoral dissertation, Ohio State University, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=osu1714964682314997

    Chicago Manual of Style (17th edition)

osu1714964682314997
© 2024, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.
Release 3.2.12