State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China.
School of Chemistry Engineering, Sichuan University of Science & Engineering, Zigong 643000, China.
Molecules. 2023 Jan 19;28(3):1007. doi: 10.3390/molecules28031007.
Linaclotide is a 14-amino acid residue peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation (IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Here we show a new method for the synthesis of linaclotide through the completely selective formation of three disulfide bonds in satisfactory overall yields via mild oxidation reactions of the solid phase and liquid phase, using 4-methoxytrityl (Mmt), diphenylmethyl (Dpm) and 2-nitrobenzyl (O-NBn) protecting groups of cysteine as substrate, respectively.
利那洛肽是一种 14 个氨基酸残基肽，经 FDA 批准用于治疗便秘型肠易激综合征（IBS-C），可激活鸟苷酸环化酶 C 以加速肠道转运。在此，我们展示了一种通过固相和液相温和氧化反应，以完全选择性方式形成三个二硫键的新方法，在令人满意的总收率下合成利那洛肽，使用 4-甲氧基三苯甲基（Mmt）、二苯甲基（Dpm）和 2-硝基苄基（O-NBn）作为半胱氨酸的保护基团。
