Polypeptide derivative and preparation method thereof
AssigneeNingbo Kunpeng Biotech Co., Ltd.
InventorsZhenshan Zhang, Song Wu, Huiling Liu, Wei Chen
Life of this patent
Estimating the term…
Abstract
The present invention discloses a polypeptide derivative, its preparation method, and pharmaceutical uses thereof. The derivative comprises a polypeptide (insulin, glucagon-like peptide-1, or PTH) and a fatty acid acyl modifying group L, which is linked to the polypeptide's lysine residue via a click reaction to yield a series of derivatives. Experimental data demonstrate that these derivatives retain biological activity while exhibiting significantly extended in vivo half-lives, and they are useful for preparing medicaments to treat or prevent diseases such as diabetes.
Claims6
A method for preparing a polypeptide derivative, comprising the following steps:
- (1) cultivating a strain containing a polypeptide coding sequence in the presence of a compound of Formula III, a pyrrolysyl-tRNA synthetase and a homologous associated tRNA thereof, wherein a lysine within the polypeptide derivative coding sequence is replaced with TAG, thereby producing a compound of Formula IV;
- then isolating or purifying the compound of Formula IV from cell culture of the strain;
- and
- wherein
- is an insulin, glucagon-like peptide-1 (GLP-1) or parathyroid hormone (PTH);
- wherein the strain is E. coli Top10 strain;
- wherein the compound of Formula IV is expressed in a form of insoluble inclusion bodies;
- wherein the insoluble inclusion bodies consist of the amino acid sequence of SEQ ID NO:
- 11, SEQ ID NO:
- 12 or SEQ ID NO:
- 13;
- (2) undertaking a reaction between the compound of Formula IV and a compound of Formula V in an inert solvent,
- wherein a, b, c, d, e and f are independent integers selected from 0 to 10;
- n is 14 in Formula V;
- thereby producing the polypeptide derivative selected from the group consisting of:
- (when a, b, c, d, e and f are all 0 in Formula V),
- (when a, b, c, d and e are all 0, and f is 2 in Formula V),
- (when a, b, c, d and e are all 0, and f is 3 in Formula V),
- (when a, b, c, d and e are all 0, and f is 4 in Formula V),
- (when a is 0, and b, c, d, e and f are all 1 in Formula V), and
- (when a, b, c, d, e and f are all 1 in Formula V),
- wherein
- is an insulin, glucagon-like peptide-1 (GLP-1) or parathyroid hormone (PTH).
Dependencies are inferred from the claim text.