Chemical synthesis and structural analysis of guanylate cyclase C agonist linaclotide

	Chemical synthesis and structural analysis of guanylate cyclase C agonist linaclotide
刊名	CHINESE CHEMICAL LETTERS
	2018
卷号	29
关键词	IRRITABLE-BOWEL-SYNDROME RACEMIC PROTEIN CRYSTALLOGRAPHY X-RAY STRUCTURES GASTROINTESTINAL-TRACT PREVALENCE LIGATION PATTERNS IMPACT Linaclotide Guanylyl cyclase Protein chemical synthesis Fmoc solid phase peptide synthesis Racemic crystallization
ISSN号	1001-8417
英文摘要	Guanylate cyclase C (GC-C) is an important receptor protein expressed by intestinal epithelial cells, and its dysregulation leads to severe intestinal diseases. Linaclotide is a 14-amino acid 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. Drug molecule design based on structural information plays a crucial role and the activity of linaclotide still need to improve, while the structure of linaclotide remains unknown. In this work, linaclotide and its D-enantiomer were obtained through Fmoc solid phase peptide synthesis method and co-crystalized through racemic crystallization. The crystal structure showed that linaclotide has a tight, three-beta turns structure immobilized by three pairs of disulfide bonds. (C) 2018 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
资助项目	[National Natural Science Foundation of China (NSFC)] ; [Fundamental Research Funds for the Central Universities]
语种	英语
CSCD记录号	CSCD:6275732
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/63642]
专题	中国科学院合肥物质科学研究院
推荐引用方式 GB/T 7714	. Chemical synthesis and structural analysis of guanylate cyclase C agonist linaclotide[J]. CHINESE CHEMICAL LETTERS,2018,29.
APA	(2018).Chemical synthesis and structural analysis of guanylate cyclase C agonist linaclotide.CHINESE CHEMICAL LETTERS,29.
MLA	"Chemical synthesis and structural analysis of guanylate cyclase C agonist linaclotide".CHINESE CHEMICAL LETTERS 29(2018).