GLP-2类多肽药物的精准糖基化修饰及其活性和稳定性研究

短肠综合征（简称SBS）是患有慢性炎症性肠病或先天性肠异常的病人通过手术切除了大部分的小肠后引起的一系列病症。GLP-2的类似物多肽Teduglutide是目前治疗SBS的主要药物之一，但它的半衰期较短。SBS病人需要每天注射一次Teduglutide，其依从性较差。.多肽和蛋白质药物在糖基化修饰后，其稳定性会增强，药动和药代性质得到极大的改善。聚乙二醇修饰（PEGylation）是开发长效化多肽和蛋白质药物时使用最广泛的技术，但传统的PEG修饰方法的位点选择性较低，得到的PEGylation产物不均一。采用定点糖基化-PEG修饰技术能解决这个难题。.我们希望使用固相多肽合成技术结合酶催化法，在Teduglutide上进行定点精准的糖基化和糖基化-PEG修饰，以获得半衰期更长的GLP-2类似物。开发出有自主知识产权的长效化GLP-2类药物，解决病人需要频繁注射的痛点，提升他们的的生活质量。

Short bowel syndrome (SBS) is a series of diseases caused by patients with chronic inflammatory bowel disease or congenital bowel abnormalities after surgical removal of most of the small intestine. Teduglutide, an analog of GLP-2, is currently one of the main drugs for the treatment of SBS, but its half-life is relatively short. SBS patients need to inject Teduglutide once a day, and their compliance is poor..After glycosylation modification of peptide and protein drugs, their stability will be enhanced, and their pharmacokinetics and pharmacokinetic properties will be greatly improved. Polyethylene glycol modification (PEGylation) is the most widely used technology for the development of long-acting peptide and protein drugs, but the traditional PEG modification methods have low site selectivity and the resulting PEGylation products are not uniform. The use of site-specific glycosylation-PEG modification technology can solve this problem..We hope to use solid-phase peptide synthesis technology combined with enzymatic catalysis to perform site-specific and precise glycosylation and glycosylation-PEG modification on Teduglutide to obtain GLP-2 analogs with a longer half-life. Developed long-acting GLP-2 drugs with independent intellectual property rights to solve the pain points of patients who need frequent injections and improve their quality of life.