Exendin 4 Conjugation and Sequence Modification to Treat Type 2 Diabetes and Obesity

<p>This thesis addresses three primary questions based on the pharmacodynamics (PD) or pharmacokinetics</p> <p>(PK) of the diabetes drug exendin 4 (Ex-4), and vitamin B12 (B12) bioconjugates, thereof.</p> <p>Q1. (Chapter 2) What effect does B12 conjugation to Ex-4 have on agonism of the glucagon-like peptide-1</p> <p>receptor (GLP-1R) in vitro and on PD/PK (including brain uptake and function) in vivo?</p> <p>Goal: To remove side-effects (nausea, weight loss) of Ex-4 without loss of glucoregulation.</p> <p>Q2. (Chapter 3) Can B12 dietary uptake proteins such as gastric intrinsic factor offer protection to B12</p> <p>conjugated peptides or proteins (focusing on Ex-4), with a view to improving in vivo PK?</p> <p>Goal: To demonstrate (in vivo) that IF binding of B12-Ex-4 confers protection against gastric</p> <p>proteolysis as a road-map to oral peptide delivery.</p> <p>Q3. (Chapter 4) Can a dual agonist of the GLP-1R and neuropeptide Y2 receptor, based on the Ex-4 primary</p> <p>amino acid sequence, be designed and validated in vitro and in vivo.</p> <p>Goal: To create a new therapeutic to simultaneously treat diabetes and obesity.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Year

2016

Author dc:creator

• Bonaccorso, Ronald Bonaccorso

Contributors dc:contributor

• Robert P. Doyle

• Physical Sciences and Mathematics

Repository record dc:identifier

https://surface.syr.edu/etd/562

OAI identifier oai:identifier

oai:surface.syr.edu:etd-1562