GlaxoSmithKline , Platform Technology & Science , 200 Cambridgepark Drive , Cambridge , Massachusetts 02140 , United States.
ACS Comb Sci. 2018 May 14;20(5):251-255. doi: 10.1021/acscombsci.8b00009. Epub 2018 Apr 25.
Encoded library technology (ELT) is an effective approach to the discovery of novel small-molecule ligands for biological targets. A key factor for the success of the technology is the chemical diversity of the libraries. Here we report the development of DNA-conjugated benzimidazoles. Using 4-fluoro-3-nitrobenzoic acid as a key synthon, we synthesized a 320 million-member DNA-encoded benzimidazole library using Fmoc-protected amino acids, amines and aldehydes as diversity elements. Affinity selection of the library led to the discovery of a novel, potent and specific antagonist of the NK3 receptor.
编码文库技术（ELT）是发现生物靶标新型小分子配体的有效方法。该技术成功的关键因素是文库的化学多样性。本文报道了 DNA 偶联苯并咪唑的开发。我们以 4-氟-3-硝基苯甲酸为关键合成子，采用 Fmoc 保护的氨基酸、胺和醛作为多样性元件，合成了一个包含 3.2 亿个成员的 DNA 编码苯并咪唑文库。文库的亲和选择导致发现了一种新型、有效和特异的 NK3 受体拮抗剂。
