Department of Chemistry, University of Richmond, Gottwald Science Center B-100 138 UR Drive University of Richmond, VA 23173, United States.
Department of Chemistry, University of Richmond, Gottwald Science Center B-100 138 UR Drive University of Richmond, VA 23173, United States.
Bioorg Med Chem. 2024 Mar 15;102:117663. doi: 10.1016/j.bmc.2024.117663. Epub 2024 Mar 1.
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.
我们报告了一种新的基于噁唑的可裂解连接子的开发，用于从附着的货物中释放肽。噁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）的存在下可以迅速断裂。可以通过标准的固相肽偶联反应合成噁唑连接子并将其连接到肽上。这些肽-噁唑缀合物的裂解在包含各种天然和非天然氨基酸的广泛肽范围内得到了证明。这些结果代表了通过单电子氧化裂解的基于肽的连接子的第一个实例。噁唑也被证明是一种合适的连接子，可用于从共轭小分子中释放肽，以及从含有多个可裂解连接子的肽中正交释放货物。噁唑连接子可以作为肽筛选平台（如肽编码文库）的有前途的工具。
