SYNTHESIS OF LIXISENATIDE WITH CAPPING Russian patent published in 2022 - IPC C07K1/06 C07K14/605 

FIELD: chemistry.

SUBSTANCE: invention relates to a method for solid-phase synthesis of polypeptide containing a predetermined amino acid sequence. In this case, the method includes cycles of binding of amino acid structural blocks to an amino acid chain, where the specified amino acid structural blocks contain an unprotected C-end carboxyl group and a protected N-end amino group, and where the specified amino acid chain contains an unprotected N-end amino group. At the same time, at least one binding cycle includes following stages: (a) binding of C-end of the amino acid structural block to the unprotected N-end amino group of the amino acid chain, so that an amide bond is formed between the amino acid chain and the amino acid structural block, (b) bringing of a product obtained at the stage (a) into contact with a capping reagent containing a capping compound, while the capping compound binds to the unprotected N-end amino group of the amino acid chain, to which, at the stage (a), no structural block was bound, and (c) removal of the protective group from N-end amino group of the amino acid structural block, where the capping reagent contains 0.5-5% vol./vol. of acetic anhydride and 0.2-2% vol./vol. of diisopropylethylamine, where polypeptide is GLP-1 agonist selected from GLP-1, exendin-3, exendin-4, and exendin-4 analogues.

EFFECT: method allows for reduction in a number of acetylated erroneous sequences occurred in peptide synthesis and increase in the yield of a product of peptide synthesis.

14 cl, 20 dwg, 30 tbl, 7 ex