Document 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.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Included in

Chemistry Commons

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