为了提高经典的肽醛类蛋白酶体抑制剂的稳定性和生物利用度,我们设计合成了4个肽缩醛和2个肽杂缩醛衍生物,并对其进行了酶水平和体外抗肿瘤实验。结果显示,4个肽缩醛化合物几乎没有显示任何活性,表明此类化合物有用作前药的潜质。而2个肽杂缩醛化合物在酶水平和细胞水平均表现出明显的活性,则表明此类化合物可能不是通过前药的形式而发挥作用,进一步优化杂环的结构,有可能发现更好的蛋白酶体抑制剂。 In order to improve the stability and bioavailability of classical peptide aldehyde proteasome inhibitors, we designed and synthesized 4 peptide acetals and 2 peptide heteroacetals, and carried out enzyme level and in vitro anti-tumor experiments . The results showed that almost none of the four peptide acetal compounds showed any activity, indicating the potential of such compounds to be useful as prodrugs. However, the two peptidic acetal compounds showed obvious activity at the enzyme level and cell level, indicating that these compounds may not play a role in the form of prodrugs, and further optimization of the structure of the heterocycle may find better Proteasome inhibitors.