Evaluating Alkaline Phosphatase-Instructed Self-Assembly of d-Peptides for Selectively Inhibiting Ovarian Cancer Cells

被引：11

作者：

Yi, Meihui ^{[1
]}

Feng, Zhaoqianqi ^{[1
]}

He, Hongjian ^{[1
]}

Dinulescu, Daniela ^{[2
]}

Xu, Bing ^{[1
]}

机构：

[1] Brandeis Univ, Dept Chem, Waltham, MA 02453 USA

[2] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 66卷 / 14期

关键词：

T-CELLS; IPILIMUMAB; CHEMOTHERAPY; MECHANISMS; EXPRESSION; RESISTANCE; NIVOLUMAB; RECEPTOR; THERAPY;

D O I：

10.1021/acs.jmedchem.3c00949

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cancer is a major public health concern requiring noveltreatmentapproaches. Enzyme-instructed self-assembly (EISA) provides a uniqueapproach for selectively inhibiting cancer cells. However, the structureand activity correlation of EISA remains to be explored. This studyinvestigates new EISA substrates of alkaline phosphatase (ALP) tohinder ovarian cancer cells. Analogues 2-8 weresynthesized by modifying the amino acid residues of a potent EISAsubstrate 1 that effectively inhibits the growth of OVSAHO,a high-grade serous ovarian cancer (HGSOC) cell line. The efficacyof 2-8 against OVSAHO was assessed, along withthe combination of substrate 1 with clinically used drugs.The results reveal that substrate 1 displays the highestcytotoxicity against OVSAHO cells, with an IC50 of around8 & mu;M. However, there was limited synergism observed betweensubstrate 1 and the tested clinically used drugs. Thesefindings indicate that EISA likely operates through a distinct mechanismthat necessitates further elucidation.

引用

页码：10027 / 10035

页数：9

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