用混合氨基酸接肽的方法合成OX型肽亚库

Study on the Synthesis of OXn Peptide Sublibraries Using Mixed Amino Acids Protocol

肽库合成是药物研究组合化学策略的重要技术之一。建立合成OX型肽亚库的固相合成方法 ,接肽反应采用等摩尔的Fmoc氨基酸混合物和DIC HOBt缩合方法 ,以高浓度的缩合剂和不断缩减溶剂的策略促进偶联反应进行完全。产物的氨基酸组成分析结果显示 ,所使用的常见氨基酸都能以相近的摩尔比例接肽至X位置。推测经多次接肽后最终形成的肽亚库中 ,含低活力氨基酸较多的肽其浓度虽然会较低一些 ,但影响不会太大 ,且本合成方法成本相对较低 ,故可为抗原表位分析、多肽药物筛选及构效关系分析提供一种有用的工具.

Peptide library is one of the important techniques of combinatorial chemistry widely used for drug discovery.In an effort to synthesis OXn peptide sublibraries,we have studied a equimolarly mixed amino acids coupling protocol.The result reveals that all the amino acids were coupled to X position in an ratio closed to equimole.Although the concentration of some peptides would be lower than others in the final products,this method still provide a useful tool for the studing of antigen epitope,screening of peptide drug and the study of structure-function.;