聚乙二醇对生长激素释放肽的化学修饰

Modification of growth hormone releasing peptide with PEG

目的为得到生长激素释放肽-2(growth hormone releasing peptide-2,GHRP-2)的聚乙二醇(mPEG)修饰产物并考察其稳定性。方法采用mPEG-NHS活性酯,在不同的溶剂条件下,用不同的投料比对GHRP-2进行修饰;HPLC检测反应结果;Sephadex 75凝胶层析法进行分离纯化。结果确定以无水二甲基甲酰胺为溶剂,m(PEG-NHS)∶m(GHRP-2)=1∶1为最佳条件,原料基本消失,主要得到单修饰的GHRP-2。所得产物在pH7.4、pH8.4、pH9.4缓冲液中50 d时的释药率分别为2.1%、7.2%、20.5%。结论无水条件更有利于mPEG-NHS活性酯对GHRP-2的修饰,产物在体外弱碱性条件下较稳定。

Objective To synthesize and characterize the prodrugs of growth hormone releasing peptide-2（GHRP-2）PEG.Methods GHRP-2 was modified by mPEG-NHS in different solution with different molar ratio of GHRP-2 to mPEG-NHS.HPLC method was used for the determination of products and GHRP-2 concentration.The products were isolated from the reaction mixture by Superdex 75 column.Results The mono-PEGylated GHRP-2 was got as the main product with the molar ratio of GHRP-2 to mPEG-NHS as 1∶ 1 in dry DMF.Drug releasing rates from mono-PEGylated GHRP-2 in buffer pH7.4,pH8.4 and pH9.4 were 2.1%,7.2% and 20.5% respectively within 50 days.Conclusions Anhydrous reaction conditions are better for the modification of GHRP-2 by mPEG-NHS.The products show stability in weak alkaline solution.