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Chemical synthesis and structural analysis of guanylate cyclase C agonist linaclotide
- Source :
- Chinese Chemical Letters. 29:1135-1138
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- 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.
- Subjects :
- chemistry.chemical_classification
Agonist
010405 organic chemistry
medicine.drug_class
Peptide
General Chemistry
Guanylate cyclase C
010402 general chemistry
01 natural sciences
Chemical synthesis
0104 chemical sciences
chemistry.chemical_compound
chemistry
Biochemistry
Peptide synthesis
medicine
Enantiomer
Receptor
Linaclotide
Subjects
Details
- ISSN :
- 10018417
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Chinese Chemical Letters
- Accession number :
- edsair.doi...........0c433eeb47f920c1c8624ed7fdfded65