By PEG modification, not only albumin is closely bound and the hydrolysis site for DPP-4 enzyme is masked, but also renal excretion is reduced, biological half-life is prolonged and a long circulation effect is achieved
Raised the temperature of the reaction mixture to 25-30C and stirred for 3 hr at the same temperature
Moreover, 6-12 repeated procedures make the experimental process cumbersome
Soluble Hydrophobic-Support-Assisted Liquid-Phase Synthesis Another innovative approach involves a soluble hydrophobic-support-assisted liquid-phase synthetic method
This action not only aids in reducing caloric intake by enhancing feelings of satiety and reducing hunger but also helps in slowing down gastric emptying, which contributes to prolonged feelings of fullness
and the generation of racemization impurities is greatly reduced, especially formation of [D-His1]-semaglutide is greatly reduced, formation of deletion peptides or polyaminopeptides in conventional one-by-one coupling, especially generation of [+Ser11]-semaglutide, [+Ala19]-semaglutide and [+Gly29]-semaglutide impurities, is effectively avoided, the purity of crude peptides is improved, downstream purification is facilitated, the material cost is greatly reduced, and the solid-phase synthesis method of the semaglutide is suitable for industrial production, and the total yield reaches 35%.
