Degree Type
Honors Capstone Project
Date of Submission
Spring 5-1-2013
Capstone Advisor
Professor Robert Doyle
Honors Reader
Professor James Kallmerten
Capstone Major
Chemistry
Capstone College
Arts and Science
Audio/Visual Component
no
Capstone Prize Winner
no
Won Capstone Funding
yes
Honors Categories
Sciences and Engineering
Subject Categories
Chemistry
Abstract
Currently patients with diabetes receive most of their treatments, including insulin, subcutaneously. Developing a method to orally deliver proteins, peptides, and potentially other therapeutics has the ability to increase patient compliance by making treatments easier to administer. Utilizing the Vitamin B12 uptake pathway is one proposed method of oral delivery of protein therapeutics. We investigated a way to synthesize a carboxylic acid derivative of Vitamin B12 (B12) that could increase the ease of its conjugation to proteins and peptides. The 5’-position of the ribose tail of B12 was oxidized using excess 2-iodoxybenzoic acid (IBX) and 2-hydroxypyridine (HYP). The synthesis of this B12 derivative allows for peptides, proteins, and other molecules to be conjugated to the 5’-position of the ribose tail of B12 using an amide bond instead of a carbamate bond. Conjugation of a simple amine-containing organic molecule, benzylamine , to this B12 derivative with a 40% yield supported the synthesis of the derivative and its potential to increase the yield of B12 conjugate formation. We also investigated a method to recombinately express C-peptide using a SUMO system and Escherichia coli. The ability to deliver C-peptide orally using the vitamin B12 uptake pathway would be an easy treatment to potentially reduce diabetic neuropathy, a complication present in many patients with diabetes.
Recommended Citation
Bernstein, Jamie L., "The Conjugation of Protein and Peptide Therapeutics to Vitamin B12 for the Oral Treatment of Diabetes" (2013). Honors Capstone Projects - All. 59.
https://surface.syr.edu/honors_capstone/59
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
