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Instructed-Assembly of Small Peptides Inhibits Drug-Resistant Prostate Cancer Cells.

Zhaoqianqi FengHuaimin WangMeihui YiChieh-Yun LoAshanti SalleeJer-Tsong HsiehBing Xu
Published in: Peptide science (Hoboken, N.J.) (2019)
Despite multiple new-drug approvals in recent years, prostate cancer remains a global health challenge because of the prostate cancers are resistant to androgen deprivation therapy. Here we show that a small D-phosphopeptide undergoes prostatic acid phosphatase (PAP)-instructed self-assembly for inhibiting castration-resistant prostate cancer (CRPC) cells. Specifically, the installation of phosphate at the C-terminal of a D-tripeptide results in the D-phosphopeptide. Dephosphorylating the D-phosphopeptide by PAP forms uniform nanofibers that inhibit VCaP, a castration-resistant prostate cancer cell. A non-hydrolyzable phosphate analogue of the D-phosphopeptide, which shares similar self-assembling properties with the D-phosphopeptide, confirms that PAP-instructed assembly is critical for the inhibition of VCaP. This work, for the first time, demonstrates PAP-instructed self-assembly of peptides for selective inhibiting castration-resistant prostate cancer (CRPC) cells.
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