JOURACA_SP_2017
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Development of Small Molecule Chemical Probes<br />
for Serine/Threonine Protein Phosphatase 5<br />
Madison Tuttle<br />
Recent studies have shown that the overexpression<br />
of serine/threonine protein<br />
phosphatase 5C (PP5C) is associated with<br />
invasive ductal carcinoma of the breast,<br />
cancer cell proliferation, and resistance to<br />
apoptosis. However, scientists currently<br />
lack the molecular equipment with which<br />
to further characterize the biological and<br />
pathological roles of PP5C in the antitumor<br />
activity of breast cancer. Previous<br />
high-throughput screening (HTS) efforts<br />
revealed two potentially selective and potent<br />
small molecule chemical probes for<br />
PP5C, containing either a 6,7-<br />
dimethoxyisoquinoline core or a 1,4-<br />
naphthoquinone core. Several analogs<br />
were synthesized and evaluated by means<br />
of a homogenous fluorescence intensitybased<br />
(HFIB) assay in %inhibition at 50 ?<br />
M. It was determined that the 6,7-<br />
dimethoxyisoquinoline series was more<br />
potent relative to the 1,4-naphthoquinone<br />
series at 50 ?M concentrations. Based on a<br />
structure-activity relationship (SAR) analysis,<br />
future analogs are being developed<br />
containing the 6,7-dimethoxyisoquinoline<br />
core to increase %inhibition at lower concentrations.<br />
Department of Chemistry<br />
Mentor: Larry Yet<br />
Chemistry<br />
46
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