Engineering novel peptide agonists of the glucagon-like peptide-1 receptor
Abstract/Contents
- Abstract
- Understanding the molecular operations of G-protein coupled receptors and their ligands is a central goal in the project of understanding human physiology and altering it with pharmacological agents to improve human health. Receptors in GPCR class B have pharmacological and structural features that are distinct among GPCRs because they are evolutionarily adapted to bind and respond to short, alpha-helical peptide ligands instead of small molecule ligands. The glucagon-like peptide-1 receptor (GLP-1R) is a class B G-protein coupled receptor and diabetes drug target expressed mainly in the pancreatic β-cells that, when activated by its agonist GLP-1 after a meal, triggers insulin secretion and β-cell survival and proliferation. The best-studied agonist peptides, GLP-1 and exendin-4, share sequence homology at their N-terminal region; however, modifications to this region that can be tolerated are not fully understood. In this work, I have used combinatorial peptide screening coupled with chemical exploration with non-canonical amino acid substitutions to find novel and highly active GLP-1R agonists with altered N-terminal composition and to explore the principles that govern peptide activity.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Longwell, Chelsea Kliebert |
|---|---|
| Degree supervisor | Cochran, Jennifer R |
| Thesis advisor | Cochran, Jennifer R |
| Thesis advisor | Chen, James Kenneth |
| Thesis advisor | Fordyce, Polly |
| Thesis advisor | Grimes, Kevin D |
| Degree committee member | Chen, James Kenneth |
| Degree committee member | Fordyce, Polly |
| Degree committee member | Grimes, Kevin D |
| Associated with | Stanford University, Department of Chemical and Systems Biology. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Chelsea Kliebert Longwell. |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Chelsea Kliebert Longwell
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...