Graduation Year

2019

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Chemistry

Major Professor

Jianfeng Cai, Ph.D.

Committee Member

James Leahy, Ph.D.

Committee Member

Wayne Guida, Ph.D.

Committee Member

Cheng, Feng, Ph.D.

Keywords

amylin, MPP8, diabetes, hIAPP, peptidomimetics, protein-protein interaction, γ-AApeptide

Abstract

Proteins can be described as the “machineries” responsible for almost all tasks in the levels of organizational complexity in multi-cellular organisms namely: the cells, tissues, organs and systems. Any disorder in the function of a protein at any of these levels could result in disease, and a study of protein function is critical to understanding the pathological features of the disease at the molecular level. A quick glance at these abundantly present proteins reveals two striking features: large diversity of biological function, and the variations in structural complexity, which varies from simple random coils, to turns and helices, and on to structured assemblies of turns, helices and sheets.

Over the past few years, more research efforts have been channeled to the application of synthetic research to protein dynamics, most especially in disease conditions. This provides insight into the design and development of chemical tools capable of modulating protein functions .Some of such tools include small molecules, peptides and peptidomimetics.

In this work, we have described the application of these tools to three (3) different disease systems topping the list of incurable diseases: HIV, Diabetes, and Cancer. We have designed and developed chemical probes to facilitate a better understanding of major “culprit” proteins underlying the pathological conditions associated with these diseases. Our designed chemical probes were capable of modulating protein functions by producing the desired effects: inhibition of protein-protein interactions.

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