环六肽Desotamide B的合成条件优化及其抑菌活性分析

Optimization of synthesis conditions of hexapeptide Desotamide B and antimicrobial activity

摘要:

在Fmoc固相合成基础上，通过对直链肽上氨基酸的活化程度和缩合试剂种类的选择优化，将直链肽的合成纯度提高到86.3%，较优化前提高了28%，并省去直链肽的分离纯化步骤。对于带侧链保护基的环肽，采用凝胶柱替代高效液相色谱进行分离，减少产物损失，将环肽总产率提高到55.6%。利用1HNMR、13CNMR和HRMS对其结构进行表征。以万古霉素为对照，对合成的Desotamide B的抗菌活性进行测试，结果表明，该化合物对革兰氏阳性菌有着较好的抑制作用，最小抑菌浓度均为16 μg/mL。

Abstract:

On the basis of Fmoc solid-phase synthesis, by optimizing the degree of activation of amino acids on linear peptides and the selection of condensation reagents, the synthesis purity of linear peptide was increased to 86.3%, higher than that before optimization 28%, the separation and purification of linear peptide was omitted. For cyclic peptides with side chain protecting groups were separated by gel column instead of high performance liquid chromatography to reduce product loss and increase the total yield of cyclic peptide to 55.6%. Their structures were characterized by 1HNMR, 13CNMR and HRMS. The antimicrobial activity of Desotamide B synthesized by the above method was tested with vancomycin as the control. The results showed that the compound had a good inhibitory effect on Gram-positive bacteria, and the minimum inhibitory concentration was 16 μg / mL.