Graduation Year

2003

Document Type

Thesis

Degree

M.S.

Degree Granting Department

Chemistry

Major Professor

Merkler, David

Keywords

enzyme, prostate, inhibition, 4-hpr, kinetics

Abstract

C-Terminal glycine-extended prohormones are enzymatically converted to á-amidated peptides, by peptidylglycine á-amidating monooxygenase (PAM). PAM is a bifunctional enzyme with two catalytic domains: peptidylglycine á -hydroxylating monooxygenase (PHM) and peptidylglycine peptidylglycineaminoglycolate lyase (PAL). PAM has a significant role in the proliferation of androgen-independent prostate cancer. Thus, the inhibition of PAM could halt cancer growth. Hippurate and hippurate analogs were used as lead compounds for developing inhibitors for PAM. The hippurate analogs exhibiting the highest affinity to PAM (lowest inhibition constant) did inhibit the growth of human androgen-independent prostate cancer DU 145 cells.

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