Citation: Chen Chenchen, Gao Shuai, Qu Qian, Mi Pengcheng, Tao Anjin, Li Yi-Ming. Chemical synthesis and structural analysis of guanylate cyclase C agonist linaclotide[J]. Chinese Chemical Letters, ;2018, 29(7): 1135-1138. doi: 10.1016/j.cclet.2018.01.005 shu

Chemical synthesis and structural analysis of guanylate cyclase C agonist linaclotide

Chen Chenchen ^a,b ,
Gao Shuai ^c ,
Qu Qian ^c ,
Mi Pengcheng ^d ,
Tao Anjin ^d ,
Li Yi-Ming ^c,,

a.
High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China
b.
School of Life Sciences, University of Science and Technology of China, Hefei 230026, China
c.
School of Biological and Medical Engineering, Hefei University of Technology, Hefei 230009, China
d.
Hybio Pharmaceutical Co., Ltd., Shenzhen 518057, China

Corresponding author: Li Yi-Ming, ymli@hfut.edu.cn
Received Date: 20 November 2017
Revised Date: 8 December 2017
Accepted Date: 4 January 2018
Available Online: 5 July 2018

Figures(4)

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.
- Linaclotide,
- Guanylyl cyclase,
- Protein chemical synthesis,
- Fmoc solid phase peptide synthesis,
- Racemic crystallization
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