We report the development of a new oxazole-based cleavable linker to release peptides from attached cargo. Oxazoles are stable to most reaction conditions, yet they can be rapidly cleaved in the presence of single-electron oxidants like cerium ammonium nitrate (CAN). An oxazole linker could be synthesized and attached to peptides through standard solid-phase peptide coupling reactions. Cleavage of these peptide-oxazole conjugates is demonstrated on a broad scope of peptides containing various natural and unnatural amino acids. These results represent the first example of a peptide-based linker that is cleaved through single-electron oxidation. The oxazole is also demonstrated to be a suitable linker for both the release of a peptide from a conjugated small molecule and the orthogonal release of cargo from a peptide containing multiple cleavable linkers. Oxazole linkers could serve as a promising tool for peptide screening platforms such as peptide-encoded libraries.

中文翻译：

---

开发基于恶唑的可裂解肽接头

我们报告了一种新的基于恶唑的可裂解接头的开发，用于从附着的货物中释放肽。恶唑在大多数反应条件下都很稳定，但在单电子氧化剂（如硝酸铈铵 (CAN)）存在下可以快速裂解。可以合成恶唑接头并通过标准固相肽偶联反应将其连接到肽上。这些肽-恶唑缀合物的裂解在含有各种天然和非天然氨基酸的多种肽上得到证实。这些结果代表了通过单电子氧化裂解的基于肽的接头的第一个例子。恶唑也被证明是一种合适的连接体，既可以从缀合的小分子中释放肽，也可以从含有多个可裂解连接体的肽中正交释放货物。恶唑接头可以作为肽筛选平台（例如肽编码库）的有前途的工具。