两亲性结构修饰的非天然氨基酸及二肽的合成

Synthesis of Unusual Amino Acids and Dipeptides Modified with Amphipathic Betaine

目的合成两亲性结构修饰的非天然氨基酸和二肽。方法将具有两亲性结构特点的甜菜碱的羧基活化成酰氯,然后与对氨基苯丙氨酸的侧链氨基反应,制备甜菜碱修饰的非天然氨基酸构建单元和目标二肽,并进行油水分配系数的测定。结果得到了1个甜菜碱修饰的非天然氨基酸和2个甜菜碱修饰的二肽。结论甜菜碱修饰的二肽具有更强的两亲性,为增强药物两亲性,改善药学性质提供了一种新的选择。

Objective To synthesize unusual amino acid and dipeptides modified with an amphipathicstructure. Methods The amphipathic betaine was activated as N-chlorobetainyl chloride and then coupled with ω-a-mino of 4-amino phenylalanine to synthesize the target compound. The peptides were synthesized in the sold phase.Results One betaine-modified non-natural amino acid and two dipeptides were obtained. Conclusion One unusualamino acid and two dipeptides modified with betaine were synthesized. The carboxyl of betaine was activated withacyl chlorides and the reactivity of betaine was greatly increased. Betaine could smoothly couple with ω-amino ofamino acid, which provided a novel alternative for the amphipathic modification of peptides.