Novel exendin agonist formulations and methods administration thereof
A technology of agonists and preparations, applied in pharmaceutical formulations, hormone peptides, drug combinations, etc., can solve problems such as the unique properties of hindered peptides and proteins
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Embodiment 1-e
[0154] Preparation of Example 1-exendin-3 His Ser Asp Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Met GluGlu Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly GlyPro Ser Ser Ser Gly Ala Pro Pro Pro Ser-NH 2 [SEQ.ID.NO.1]
[0155]Using Fmoc-protected amino acid (Applied Biosystems, Inc.) in 4-(2'-4'-dimethoxyphenyl)-Fmocaminomethylphenoxyacetamide norleucine MBHA resin (Novabiochem, 0.55 mmole / g) to synthesize the above amide peptide. In general, one coupling cycle was used throughout the synthesis, and Fast Moc (HBTU activated) chemistry was utilized. The extended peptide chain was deprotected (removal of the Fmoc group) using piperidine. Finally, triethylsilane (0.2 mL), ethanedithiol (0.2 mL), anisole (0.2 mL), water (0.2 mL) and trifluoroacetic acid were applied according to standard methods (Introduction to Lysis Technology, Applied Biosystems, Inc.) (15 mL) of the mixture to deprotect the completed peptide resin. The peptide was precipitated with ether / w...
Embodiment 2
[0158] Example 2- Preparation of exendin-4 His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Met GluGlu Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly GlyPro Ser Ser Ser Gly Ala Pro Pro Pro Ser-NH 2 [SEQ.ID.NO.2]
[0159] Using Fmoc-protected amino acid (Applied Biosystems, Inc.) in 4-(2'-4'-dimethoxyphenyl)-Fmocaminomethylphenoxyacetamide norleucine MBHA resin (Novabiochem, 0.55 mmole / g) to assemble and synthesize the above amide peptide, according to the method similar to that of exendin-3 described in Example 1, the peptide was cleaved from the resin, deprotected and purified. Solvent A (0.1% TFA in water) and solvent B (0.1% TFA in ACN) were used in the analysis. Analytical RP-HPLC (gradient 36%-46% solvent B in solvent A in 30 minutes) of the lyophilized peptide gave the product peptide with an observed retention time of 14.9 minutes. Electron spray mass spectrometry (M): the calculated value is 4186.6; the measured value is 8186.0-4186.8 (four ba...
Embodiment 3
[0160] Embodiment 3-exendin-4 in Gila deformity lizard body
[0161] circulating diet-associated peptide
[0162] This experiment is to investigate whether exendin-4 has a metabolic effect in the Gila deformity lizard itself. To investigate whether exendin-4 is present in the blood of Gila teratophiles under the influence of feeding, blood was taken from a lizard fasted for 7 weeks, before and 30 minutes after feeding a small rat. Full-length exendin-4 in plasma was analyzed using immunoradiometric assays of monoclonal antibody pairs directed against exendin-4 N-terminal and C-terminal epitopes. The plasma concentration of exendin-4 in fasted lizards was 76pg / mL, close to the lower limit of quantitation. After eating, the plasma concentration increased 300-fold to 23,120 pg / mL.
[0163] In a second experiment, 2 lizards were fasted for 5 weeks and serial blood samples were taken before and after feeding 1 or 2 small rats (47-49 g). Immediately af...
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