Date of Award

5-27-2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioinformatics

First Advisor

Cesar Compadre

Abstract

Vitamin E is composed of two series of closely related compounds, tocopherols and tocotrienols, which show a widely varying degree of biological effectiveness. In recent years, the tocotrienols have gained considerable attention because of their beneficial effects in areas such as cholesterol reduction, neuroprotection, radiation protection and cancer treatment and prevention. Unfortunately, the potential of the tocotrienols has been hampered because their short circulation half-life that limits their bioavailability. The short circulation half-life of the tocotrienols is related to their low affinity for the &alpha,-tocopherol transfer protein, the protein responsible for maintaining the plasma level of the vitamin E. Tocotrienols have less affinity for ATTP as compared to &alpha,-tocopherol. We hypothesized that the low-binding affinity of tocotrienols to ATTP is directly related to the relatively more rigid tail structure of the tocotrienols in comparison to that of the &alpha,-tocopherol. Therefore, compounds with a more flexible tail would have better binding to ATTP and consequently would have better bioavailability. Based on this hypothesis we developed of a new class of tocotrienol analogues, the tocoflexols, which maintain the bioactivity level of the tocotrienols with the potential to achieve the bioavailability of the &alpha,-tocopherol. By maintaining the bioactivity of the tocotrienols while achieving enhanced bioavailability, these compounds may have a strong potential as therapeutic agents.

Download

Share

COinS