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Determination Of Novel Metabolites Of Therapeutic Agents Used In The Treatment Of Castration-Resistant Prostate Cancer, Mohammad Alyamani
Determination Of Novel Metabolites Of Therapeutic Agents Used In The Treatment Of Castration-Resistant Prostate Cancer, Mohammad Alyamani
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Despite an array of improved treatment options over the past decade, prostate cancer remains the second leading cause of cancer mortality for men in the United States. Abiraterone and galeterone are oral steroidal compounds that are used to treat metastatic castration-resistant prostate cancer (CRPC). Abiraterone blocks 17a-hydroxylase/17,20-lyase (CYP17A1), an enzyme required for androgen synthesis. Galeteron inhibits CYP17A1, blocks the androgen receptor (AR), and decreases AR protein levels. Both drugs share the same structure with endogenous androgens such as dehydroepiandrosterone, which are substrates for the enzyme, 3ß-hydroxysteroid dehydrogenase (3ßHSD). Metabolites of 3ßHSD undergo further metabolism to produce the AR ligand, testosterone …
Using Nucleotide Analogs As Biochemical Probes To Evaluate The Mechanisms Involved In Translesion Replication By A High Fidelity Dna Polymerase, Anvesh Dasari
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Translesion DNA synthesis (TLS) allows DNA polymerases to incorporate nucleotides opposite and beyond damaged DNA. This activity is an important risk factor for the initiation and progression of genetic diseases including cancer. My study evaluates the ability of a high-fidelity DNA polymerase to perform TLS with 8-oxo-guanine, a pro-mutagenic DNA lesion formed by reactive oxygen species. Using modified purine and non-natural indole analogs as biochemical probes, I have evaluated the influence of desolvation, hydrogen bonding interactions, and shape complementarity towards nucleotide binding and incorporation opposite the miscoding lesion 8-oxo-guanine by the high fidelity gp43exo- DNA polymerase. In Chapter II, I …