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Glucagon-like peptide-2 analogue, its preparation method and application
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A technique for glucagon and analogs, applied in the field of glucagon-like peptide-2 analogs and their preparation and use, can solve the problems of inconclusive GLP-2 intestinal tumor and the like
Inactive Publication Date: 2013-02-27
JIANGSU HANSOH PHARMA CO LTD
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Problems solved by technology
It has been confirmed that GLP-2 has the effect of promoting nutrient absorption, but whether it can reduce intestinal damage and promote intestinal repair has yet to be confirmed by further clinical trials
Although the adverse effects of GLP-2 have not been found during the treatment, considering that the biological role of GLP-2 was found in the study of glucagon-induced tumors in animals, and the study of subcutaneous injection of glucagon in nude mice It has been shown that GLP-2 significantly promotes the growth of intestinal mucosa, so whether GLP-2 stimulates the growth of intestinal tumors is still inconclusive
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Embodiment 1
[0054] Example 1 Solid-phase synthesis of positive compound Teduglutide
[0055] The sequence of the positive compound Teduglutide is:
[0057] (1) Drying and swelling of solid-phase synthetic resin
[0058] Weigh 40g (20mmol) of Fmoc-Asp(OtBu)-Wang resin (0.5mmol / g) dried in vacuum for 24 hours and place it in a 2L bubbling bottle, add 400mL of DMF swelling resin for 30 minutes, and remove the DMF solution;
[0059] (2) Fmoc-Asp(OtBu)-Wang resin to remove Fmoc protecting group
[0060] 200 mL of 20% piperidine / DMF solution was added to the bubbling bottle containing Fmoc-Asp(OtBu)-Wang resin, and the solution was drawn out after 5 minutes of reaction, and then 200 mL of 20% piperidine / DMF solution was added to react at room temperature for 20 minutes. After the reaction was completed, the resin was washed four times with 200 mL...
Embodiment 2
[0072] Example 2 Solid-phase synthesis of compound 1
[0073] The sequence of compound 1 is:
[0074] D-His-Gly-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu-Ala-Ala-Arg-Asp-Phe-Ile-Asn- Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-OH, that is, in the general formula (I), X1 is D-His, X2 is Gly, X3 is ASP, X10 is Met, and X11 is Asn , X15 is Asp, X16 is Asn, X24 is Asn, and X25 is Trp.
[0075] The preparation method is the same as in Example 1.
Embodiment 3
[0076] Example 3 Solid-phase synthesis of compound 2
[0077] The sequence of compound 2 is:
[0078]D-His-Gly-Glu-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu-Ala-Ala-Arg-Asp-Phe-Ile-Asn- Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-OH, that is, in the general formula (I), X1 is D-His, X2 is Gly, X3 is Glu, X10 is Met, and X11 is Asn , X15 is Asp, X16 is Asn, X24 is Asn, and X25 is Trp.
[0079] The preparation method is the same as in Example 1.
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Abstract
The invention relates to a glucagon-like peptide-2 analogue, its preparation method and application. The invention relates to a glucagon-like peptide-2 (GLP-2) analogue and its medical application. The invention further relates to a medicine composition containing the GLP-2 analogue and its medicinal salts. According to the invention, the GLP-2 analogue or the medicine composition containing the GLP-2 analogue and its medicinal salts can be widely applied for preventing or treating mucosal injury-related gastrointestinal symptoms and mitigating the side effects on gastrointestinal tract caused by chemotherapy and radiation therapy.
Description
[0001] This application is a divisional application of a Chinese patent application with the application number of 200910126363.9 and the filing date of March 5, 2009, and the invention title is "Glucagon-like peptide-2 analogs and their preparation methods and uses". technical field [0002] The present invention relates to a glucagon-like peptide-2 (Glucagon Like Peptide-2, GLP-2) analog and its preparation for preventing and / or treating gastrointestinal mucosal damage-related disorders and alleviating chemotherapy and radiotherapy. Use in medicine for intestinal side effects. Background technique [0003] GLP-2 belongs to proglucagon-derived peptide (PGDP), which is one of the degradation products of proglucagon (PG) by prohormone convertase (PC). A single-chain polypeptide consisting of 33 amino acid residues with a molecular weight of 3900 Daltons, its amino acid sequence is highly conserved in mammals [Drucker DJ.Glucagon-like peptide 2.J Clin Endocrinol Metab, 2001, 8...
Claims
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