A kind of preparation method of plicanatide

Abstract

The invention discloses a preparation method of pulikanatide, comprising the following steps: 1) Fmoc-Leu-resin carrier adopts Fmoc solid-phase synthesis method according to the polypeptide sequence sequence of pulikanatide from carbon end to nitrogen end Coupling one by one to obtain peptide resins protected by side chain groups; 2) Peptide resins are sequentially deprotected according to Cys4‑Cys12 and Cys7‑Cys15 respectively, and then oriented to form a ring to obtain fully protected pulikanatide peptide resins; 3) Cleavage The reagent cleaves the peptide resin protected by the side chain group, and 4) after desalting, it is purified and freeze-dried to obtain plicanatide. The preparation process of pulikanatide adopted in the present invention has practical industrial application prospects and considerable economic and practical value.

Description

technical field

[0001] The invention belongs to the technical field of pharmacy, in particular to a method for preparing pricanatide by directional cyclization reaction on resin. Background technique

[0002] The C-type guanylate cyclase (GC-C) receptor is mainly expressed on the luminal side of small intestinal epithelial cells. GC-C is a multicenter enzyme that includes an extracellular ligand-binding domain, a single-channel transmembrane domain, an active center similar to a tyrosine kinase protein, and a C-terminal GC-C catalyzed by ligand-mediated activation to generate cGMP area. Enterotoxin (ST) causes secretory diarrhea in susceptible individuals by overactivating the signaling pathway of the gut receptor GC-C, the only ST target identified in humans. Correspondingly, knockout of the GC-C-encoding gene in mice resulted in the suppression of ST-induced intestinal secretion and diarrhea. Infectious diarrhoea caused by ST-producing bacteria is a major cause of unsan...

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