Yupeng Zheng, Baochang Zhang, Wei-Wei Shi, Xiangyu Deng, Tong-Yue Wang, Dongyang Han, Yuxiang Ren, Ziyi Yang, Yong-Kang Zhou, Jian Kuang, Zhi-Wen Wang, Shan Tang, Ji-Shen Zheng
Mirror-image proteins (D-proteins) are useful in biomedical research for purposes such as mirror-image screening for D-peptide drug discovery, but the chemical synthesis of many D-proteins is often low yielding due to the poor solubility or aggregation of their constituent peptide segments. Here, we report a Lys-C protease cleavable solubilizing-tag and its use to synthesize difficult-to-obtain D-proteins. Our tag is easily installed onto multiple amino acids such as D-Lys, D-Ser, D-Thr and/or the N-terminal D-amino acid of hydrophobic peptides, is impervious to various reaction conditions, such as peptide synthesis, ligation, desulfurization, and transition metal-mediated deprotection, and yet can be completely removed by Lys-C protease under denaturing conditions to give the desired D-protein...
February 7, 2024: Angewandte Chemie