肿瘤细胞治疗研究
英文原题：Phenylalanine-Based DNA-Encoded Chemical Libraries for the Discovery of Potent and Selective Small Organic Ligands Against Markers of Cancer and Immune Cells.
DNA编码化合物库（DELs）是药物发现的有力工具，能够针对具有药学意义的靶蛋白，对海量小分子化合物库进行高通量筛选。
DNA编码化合物库（DELs）是药物发现的有力工具，能够针对具有药学意义的靶蛋白对海量小分子库进行高通量筛选。本文描述了两个新的DEL库的合成，分别命名为FM-DEL1和FM-DEL2，分别包含7'710和5'697'690个化合物。这些库的构建方式是在苯丙氨酸中心骨架上安装一组或两组构建模块。FM-DELs针对前列腺癌和肾细胞癌的标志物，以及针对在NK 细胞表面表达的一个免疫靶标进行了筛选。针对这些靶标的DEL筛选获得了高活性和选择性的结合物，其亲和常数在纳摩尔范围内。针对肿瘤相关抗原的小分子配体被用于开发小分子放射性药物，这些药物在全身给药后选择性积聚在癌症部位。
DNA-encoded chemical libraries (DELs) are powerful tools for drug discovery, enabling the high-throughput screening of vast libraries of small molecules against target proteins of pharmaceutical interest. Here, the synthesis of two new DELs, named FM-DEL1 and FM-DEL2, including 7'710 and 5'697'690 compounds, respectively is described. These libraries are constructed by installing one or two sets of building blocks on a phenylalanine central scaffold. FM-DELs are screened against markers of prostate cancer, and renal cell carcinoma, and against an immunological target expressed on the surface of natural killer cells. Highly potent and selective binders with affinity constants in the nanomolar range are obtained from DEL screenings against those targets. Small-molecule ligands against tumor-associated antigens are used to develop small-molecule radiopharmaceuticals that selectively accumulate at cancer sites after systemic administration.
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