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.

中文翻译：

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小肽的指令组装抑制药物耐药的前列腺癌细胞。

尽管近年来获得了多种新药批准，但前列腺癌仍然对全球健康构成挑战，因为前列腺癌对雄激素剥夺疗法具有抵抗力。在这里，我们显示了一个小的D-磷酸肽经历了前列腺酸磷酸酶（PAP）指导的自组装，以抑制去势抵抗性前列腺癌（CRPC）细胞。具体而言，在D三肽的C末端安装磷酸盐会导致D磷酸肽。通过PAP对D-磷酸肽进行去磷酸化，形成均匀的纳米纤维，从而抑制了CRPC细胞VCaP。D-磷酸肽的一种不可水解的磷酸盐类似物，与D-磷酸肽具有相似的自组装特性，这证明PAP指导的组装对于抑制VCaP至关重要。这项工作是第一次