Glucagon-like peptide-1 (GLP-1) analogs, and preparation method and application thereof

• Main Authors: WANG YULI, XIA GUANGPING, ZHAO NAXIA, HAN YINGMEI
• Format: Patent
• Language: Chinese; English
• Published: 10.10.2017
• Subjects: CHEMISTRY; CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION ORPROCESSING OF GOODS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS; TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINSTCLIMATE CHANGE

The invention provides glucagon-like peptide-1 (GLP-1) analog monomer peptides. The monomer peptides have the general formula 1: Z1HAX1GTFTSDVSSYLE X2QAAKEFICWLVKGRX3, wherein Z1 is hydrogen, acetyl or trifluoroacetyl; X1 is Met, Leu, Pro, Phe or Tyr; and X2 is Gly, Glu or Aib (2-aminoisobutyric acid). The invention also provides a dimer formed by the monomer peptides, a preparation method of the dimer, and application of the dimer in preparing drugs. The dimer of the GLP-1 analog monomers provided by the invention has the obvious effect of lowering the blood sugar, and the in vivo half life can reach 12-72 hours or above, thereby solving the problem of short half life in the natural GLP-1, and greatly enhancing the clinical application compliance. 本发明提供了种胰高血糖素样肽-1类似物单体肽，所述单体肽具有通式1：ZHAXGTFTSDVSSYLE XQAAKEFICWLVKGRX；其中，Z为氢、乙酰基或三氟乙酰基；X为Met、Leu、Pro、Phe或Tyr；X为Gly、Glu或Aib(2-氨基异丁酸)。本发明还提供了由所述单体肽形成的二聚体，以及该二聚体的制备方法和在制备药物中的用途。本发明提供的GLP-1类似物单体的二聚体具有显著的降血糖作用，体内半衰期可以达到12-72小时以上，克服了天然GLP-1半衰期短的问题，可大幅提高临床应用依从性。