We report a biocompatible and rapid reaction between cysteine thiols and 2,4-difluoro-6-hydroxy-1,3,5-benzenetricarbonitrile (DFB), which enables the efficient cyclization of peptides in neutral aqueous solutions. The reaction was further applied to cyclize peptides displayed on the phage surface without reducing phage infectivity, thus affording high-quality cyclic peptide libraries useful for screening of cyclic peptide ligands. Using the DFB-cyclic peptide library, we identified ligands that can distinguish the pro-survival protein Bcl-xl from its close relative Bcl-2. Therefore, this study on one hand reports a useful reaction for the construction of cyclic peptide libraries, and on the other hand presents valuable hits for further design of selective Bcl-xl ligands.

中文翻译：

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生物相容性和2,4-二氟-6-羟基-1,3,5-苯三腈与肽的快速环化，用于开发环肽库。

我们报告了半胱氨酸硫醇和2,4-二氟-6-羟基-1,3,5-苯三甲腈（DFB）之间的生物相容性和快速反应，这使肽在中性水溶液中的有效环化成为可能。将该反应进一步应用于环化展示在噬菌体表面上的肽而不降低噬菌体的感染性，因此提供了可用于筛选环肽配体的高质量环肽文库。使用DFB环肽库，我们确定了可以区分亲生存蛋白Bcl-xl和其近亲Bcl-2的配体。因此，该研究一方面报告了用于构建环肽文库的有用反应，另一方面为进一步设计选择性Bcl-xl配体提出了有价值的建议。