A kind of synthetic method of ularitide

Abstract

The invention relates to the technical field of medicament, and discloses a synthetic method for ularitide. According to the synthetic method, the protected Tyr and an ionic liquid carrier are coupled under the action of a coupling system; according to the peptide sequence of the ularitide, residual protected amino acid is prepared through solid-phase synthesis, an ularitide linear peptide ionic liquid peptide carrier is obtained, and a linear peptide crude product is obtained through cracking; the linear peptide crude product is oxidized, and a disulfide bond-containing ularitide crude product is obtained; and the ularitide crude product is purified, and fine peptide is obtained. The room temperature ionic liquid carrier is used for replacing a resin carrier in traditional solid-phase synthesis and an organic solvent and water liquid phase oxidizing medium in the oxidization link, the purity of the crude peptide of the ularitide linear peptide obtained through solid-phase synthesis is obviously increased, meanwhile, the oxidization reaction time can be greatly shortened, operation is convenient, and generation of organic waste liquid is avoided.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a method for synthesizing ularitide. Background technique [0002] Ularitide is a natriuretic peptide isolated from human urine. Its analytical structure is similar to that of atrial natriuretic peptide, except that there are four more amino acid residues at the N-terminal of its sequence. Relevant studies have shown that Ularitide has various effects such as dilating blood vessels, dilating bronchi and diuresis, and has certain therapeutic effects on heart failure, renal failure, pulmonary hypertension and bronchial asthma clinically. [0003] The structure of Uralitide is a polypeptide composed of 32 amino acids containing a pair of intramolecular disulfide bonds, which is generally prepared by chemical synthesis. The sequence structure is: [0004] H-Thr-Ala-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Met-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly- Leu-Gly-Cys-Asn-Ser-Phe-Arg-...

AI Technical Summary

Problems solved by technology

However, using this scheme for oxidation, due to the difficulty in dissolving uraritide and the final oxidation needs to be carried out at a very dilute concentration, the operation is very difficult, and the reaction time is long, which is not conducive to large-scale production

In addition, this method will produce a large amount of mixed waste liquid of organic solvent and water, which is not conducive to the requirements of green chemistry in terms of environmental protection.

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