BYU

Abstract by Jatinder Singh

Personal Infomation


Presenter's Name

Jatinder Singh

Degree Level

Doctorate

Abstract Infomation


Department

Chemistry and Biochemistry

Faculty Advisor

Steven Castle

Title

Rendering Helical Peptides More Suitable as Anti-Cancer Agents

Abstract

Since the discovery of first peptide insulin in 1920, 7500 naturally occurring peptides have been identified. However, these peptides suffer from a major drawback of rapid digestion by enzymes, poor bioavailability, and lack of membrane permeability. Thus, they are less efficient than small-molecule drugs and very expensive. Previously, our lab successfully synthesized several medium-sized peptides (β-hairpins) of α, β-dehydroamino acids (DAAs) with 6-7 times more stability to proteolysis digestion than control peptide. Now, we are introducing DAAs in helical structures, synthesizing 310-helical peptides having conformational rigidity and thermodynamically favored folded structure. Stapling (stapled α-helical peptides, SAH) is another method to induce conformational stability in helical peptides, but recent evidences cast doubt on their suitability as drugs. We are synthesizing two DAA-containing helical peptides and then evaluating their proteolytic stability: Z-Aib-Pro-DEnv-Ala-OMe and Z-DEnv-Pro-Aib-Ala-OMe. Introduction of DAAs into helical structure could enable the future design of stabilized helical anti-cancer peptides.