STAT3 is attractive target for development of anti‐cancer therapeutics as it is implicated in nearly all forms of human tumors. To identify novel leads, we screened a combinatorial peptide library displayed on the surface of M13 bacteriophage. After three rounds of biopanning, a dodecapeptide with the YYVSWPPDMMHY sequence was found to be enriched by 36% while another with a short consensus motif was displayed in 20% of the phages. Binding analysis by isothermal titration calorimetry shows the most displayed peptide interacted with a K_d of 1.79 μM, which on modification of its structure to mimic the natural binding partners of STAT3 brought the affinity to high nanomolar range (K_d = 500 nM). Using a panel of tumor cell lines, we show that the peptides prevented the proliferation of triple‐negative breast cancer cells with a moderate activity (GI₅₀ = 50 μM). Furthermore, gene expression analysis shows the peptide reduced the expression of oncoproteins critical for tumor cell proliferation, angiogenesis, and metastasis. To find novel STAT3‐interacting proteins, we searched the non‐redundant sequences of the National Center for Biotechnology Information database which allowed us to identify potential binding partners of the protein. In sum, our data show the identified agents could serve as useful therapeutics candidates for further development.

中文翻译：

---

来自组合肽库的新型抗癌候选物。

STAT3 是开发抗癌疗法的有吸引力的目标，因为它涉及几乎所有形式的人类肿瘤。为了识别新的线索，我们筛选了一个显示在 M13 噬菌体表面的组合肽库。在三轮生物淘选后，发现具有 YYVSWPPDMMHY 序列的十二肽富集了 36%，而另一个具有短共有基序的十二肽在 20% 的噬菌体中显示。通过等温滴定量热法进行的结合分析显示，展示最多的肽与1.79 μM的K _d相互作用，通过修改其结构以模拟 STAT3 的天然结合伙伴，将亲和力提高到高纳摩尔范围（K _d = 500 纳米）。使用一组肿瘤细胞系，我们表明肽以中等活性（GI ₅₀  = 50 μM）阻止了三阴性乳腺癌细胞的增殖。此外，基因表达分析显示该肽降低了对肿瘤细胞增殖、血管生成和转移至关重要的癌蛋白的表达。为了找到新的 STAT3 相互作用蛋白，我们搜索了国家生物技术信息中心数据库的非冗余序列，这使我们能够识别蛋白质的潜在结合伙伴。总而言之，我们的数据表明，鉴定出的药物可以作为进一步开发的有用的治疗候选药物。