31results about How to "Overcoming the problem of short half-life" patented technology

The invention discloses GLP-1 analogs which have the following general formula I: 7HAEX10T FTSX15V SSYLE X22QAAK EFIX30W LX33KGR G37n1X1C n2X2, wherein X10 is glycine or cysteine, X15 is aspartic acid or cysteine, X22 is glycine or cysteine, X30 is alanine or cysteine, X33 is valine or cysteine, and at least one of X10, X15, X22, X30 and X33 is cysteine; n1X1 represents n X1s, n=3-30, and X1 is glycine, alanine or valine; n2X2 represents n X2s, n=3-30, and X2 is glycine, alanine or valine; and the two cysteines contained in the general formula I respectively form a disulfide bond. The GLP-1 analogs can effectively increase the blood half life of GLP-1, can overcome the actual state that the GLP-1 analogs can not be used clinically due to short half life, and has wide application prospects in the field of therapeutic drugs for diabetes and obesity. The invention also discloses a preparation method of the GLP-1 analogs and application thereof.

The invention discloses a polypeptide complex, which comprises GLP-1 (glucagon-like peptide-1) and a carrier polypeptide, wherein the carrier polypeptide can effectively prolong blood half life of GLP-1, thus the existing condition that GLP-1 cannot be clinically used due to short half life is overcome, and GLP-1 has better application prospects in the field of medicaments for treating diabetes and obesity. The invention also discloses a preparation method and an application of the polypeptide complex. In addition, the invention further discloses a pharmaceutical composition comprising the polypeptide complex.

The invention provides a long-acting glucagon-like peptide-1 analogue. The long-acting glucagon-like peptide-1 analogue is characterized in that the polypeptide has a structure shown as a general formula I: Z1-HX8EX10T FTSDV SSYLE X22QAAK EFIX30W LVKX35RG-Z2, wherein, any two residues of X8, X10, X22, X30, X35 are cysteine, Z2 is -H or -HN2; any one residue of X8, X10, X22, X30, X35 is cysteine, and Z2 is a -CG sequence. The glucagon-like peptide-1 analogue expressed by the general formula I always contains two cysteine residues to form an intramolecular disulfide bond, so that rapid degradation of the analogue in vivo is avoided, and the in-vivo half life is obviously prolonged.

The invention provides a GLP-1 (glucagon-like peptide-1) analogue modified with PEG (polyethylene glycol). The GLP-1analogue has an amino acid sequence shown in SEQ ID NO: 1-19, and the cysteine residue of the amino acid sequence is modified with a PEG group. The invention further provides an application of the analogue or analogue composition in preparation of drugs for treating diabetes, obesity and Alzheimer's disease. The polypeptide has better metabolism stability, has remarkably prolonged in-vivo half-life period, solves the problem that the half-life period of natural GLP-1 is short, can substantially improve the clinical application compliance and has higher application value.

The invention provides a monomer peptide of a glucagon-like peptide-1 analogue. The monomer peptide is represented by a general formula 1: Z<1>HAX<1>GTFTSDVSSYLE X<2>QAAKEFIAWLVKGRGCAX<3>, wherein Z<1> is H, acetyl or trifluoroacetyl; X<1> is Met, Leu, Pro, Phe, or Tyr; X<2> is Gly, Glu, or Aib (2-aminoisobutyric acid); and X<3> is NH<2> or H. The invention also provides a dimer formed by the monomer peptide, a preparation method of the dimer and applications of the dimer in preparing medicines. The dimer of the GLP-1 analogue monomer peptide provided by the invention has an obvious hypoglycemic effect, and the half-life in vivo can reach 12-72 hours or above, so that the problem of short half-life of natural GLP-1 is overcome and compliance of clinical application can be greatly improved.