This thesis addresses three primary questions based on the pharmacodynamics (PD) or pharmacokinetics
(PK) of the diabetes drug exendin 4 (Ex-4), and vitamin B12 (B12) bioconjugates, thereof.
Q1. (Chapter 2) What effect does B12 conjugation to Ex-4 have on agonism of the glucagon-like peptide-1
receptor (GLP-1R) in vitro and on PD/PK (including brain uptake and function) in vivo?
Goal: To remove side-effects (nausea, weight loss) of Ex-4 without loss of glucoregulation.
Q2. (Chapter 3) Can B12 dietary uptake proteins such as gastric intrinsic factor offer protection to B12
conjugated peptides or proteins (focusing on Ex-4), with a view to improving in vivo PK?
Goal: To demonstrate (in vivo) that IF binding of B12-Ex-4 confers protection against gastric
proteolysis as a road-map to oral peptide delivery.
Q3. (Chapter 4) Can a dual agonist of the GLP-1R and neuropeptide Y2 receptor, based on the Ex-4 primary
amino acid sequence, be designed and validated in vitro and in vivo.
Goal: To create a new therapeutic to simultaneously treat diabetes and obesity.
","abstract_html":"<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>","abstract_has_math":false,"creators":["Bonaccorso, Ronald Bonaccorso"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Robert P. Doyle"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-12-01T08:00:00Z","date_published":"2016-12-01T08:00:00Z","updated_at":"2026-07-24T04:55:13Z","subjects":["Physical Sciences and Mathematics"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://surface.syr.edu/etd/562","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Robert P. Doyle"]},{"key":"dc:creator","label":"Author","values":["Bonaccorso, Ronald Bonaccorso"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Physical Sciences and Mathematics"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://surface.syr.edu/etd/562"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["This thesis addresses three primary questions based on the pharmacodynamics (PD) or pharmacokinetics
(PK) of the diabetes drug exendin 4 (Ex-4), and vitamin B12 (B12) bioconjugates, thereof.
Q1. (Chapter 2) What effect does B12 conjugation to Ex-4 have on agonism of the glucagon-like peptide-1
receptor (GLP-1R) in vitro and on PD/PK (including brain uptake and function) in vivo?
Goal: To remove side-effects (nausea, weight loss) of Ex-4 without loss of glucoregulation.
Q2. (Chapter 3) Can B12 dietary uptake proteins such as gastric intrinsic factor offer protection to B12
conjugated peptides or proteins (focusing on Ex-4), with a view to improving in vivo PK?
Goal: To demonstrate (in vivo) that IF binding of B12-Ex-4 confers protection against gastric
proteolysis as a road-map to oral peptide delivery.
Q3. (Chapter 4) Can a dual agonist of the GLP-1R and neuropeptide Y2 receptor, based on the Ex-4 primary
amino acid sequence, be designed and validated in vitro and in vivo.
Goal: To create a new therapeutic to simultaneously treat diabetes and obesity.
"]},{"key":"dc:title","label":"Title","values":["Exendin 4 Conjugation and Sequence Modification to Treat Type 2 Diabetes and Obesity"]}]}],"canonical_facts":{"dc:contributor":["Robert P. Doyle"],"dc:creator":["Bonaccorso, Ronald Bonaccorso"],"dc:description.abstract":["This thesis addresses three primary questions based on the pharmacodynamics (PD) or pharmacokinetics
(PK) of the diabetes drug exendin 4 (Ex-4), and vitamin B12 (B12) bioconjugates, thereof.
Q1. (Chapter 2) What effect does B12 conjugation to Ex-4 have on agonism of the glucagon-like peptide-1
receptor (GLP-1R) in vitro and on PD/PK (including brain uptake and function) in vivo?
Goal: To remove side-effects (nausea, weight loss) of Ex-4 without loss of glucoregulation.
Q2. (Chapter 3) Can B12 dietary uptake proteins such as gastric intrinsic factor offer protection to B12
conjugated peptides or proteins (focusing on Ex-4), with a view to improving in vivo PK?
Goal: To demonstrate (in vivo) that IF binding of B12-Ex-4 confers protection against gastric
proteolysis as a road-map to oral peptide delivery.
Q3. (Chapter 4) Can a dual agonist of the GLP-1R and neuropeptide Y2 receptor, based on the Ex-4 primary
amino acid sequence, be designed and validated in vitro and in vivo.
Goal: To create a new therapeutic to simultaneously treat diabetes and obesity.
"],"dc:identifier":["https://surface.syr.edu/etd/562"],"dc:subject":["Physical Sciences and Mathematics"],"dc:title":["Exendin 4 Conjugation and Sequence Modification to Treat Type 2 Diabetes and Obesity"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T04:55:13Z"}