Instructed-assembly of small peptides inhibits drug-resistant prostate cancer cells

Zhaoqianqi Feng, Huaimin Wang, Meihui Yi, Chieh Yun Lo, Ashanti Sallee, Jer Tsong Hsieh, Bing Xu

Research output: Contribution to journalArticle

Abstract

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 CRPC 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 CRPC cells.

Original languageEnglish (US)
Article numbere24123
JournalPeptide Science
Volume112
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • drug resistance
  • enzyme
  • prostate cancer
  • selective inhibition
  • self-assembly

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

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