Acylpeptide hydrolase is a serine protease which, together with prolyl oligopeptidase, dipeptidyl peptidase IV and oligopeptidase B belongs to the prolyl oligopeptidase family. Its primary function is associated with the removal of N-acetylated amino acid residues from proteins and peptides. Although the N-acylation occurs in 50-90% of eukaryotic proteins, the precise functions of this modification remains unclear. Recent findings have indicated that acylpeptide hydrolase participates in various events including oxidized proteins degradation, amyloid β-peptide cleavage and response to DNA damage. Considering the protein degradation cycle cross-talk between acylpeptide hydrolase and proteasome, inhibition of the first enzyme resulted in down-regulation of the ubiquitin-proteasome system and induction of cancer cell apoptosis. Acylpeptide hydrolase has been proposed as an interesting target for the development of new potential anticancer agents. Here we present the synthesis of simple derivatives of (1-aminoethyl)phosphonic acid diaryl esters, phosphonic analogues of alanine diversified at the N-terminus and ester rings, as inhibitors of acylpeptide hydrolase and discuss the ability of the title compounds to induce apoptosis of U937 and MV-4-11 tumor cell lines.

中文翻译：

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作为酰基肽水解酶抑制剂的丙氨酸的膦酸类似物

酰基肽水解酶是一种丝氨酸蛋白酶，它与脯氨酰寡肽酶、二肽基肽酶 IV 和寡肽酶 B 一起属于脯氨酰寡肽酶家族。其主要功能与从蛋白质和肽中去除 N-乙酰化氨基酸残基有关。尽管 N-酰化发生在 50-90% 的真核蛋白质中，但这种修饰的确切功能仍不清楚。最近的研究结果表明，酰基肽水解酶参与各种事件，包括氧化蛋白降解、淀粉样蛋白 β-肽裂解和对 DNA 损伤的反应。考虑到酰基肽水解酶和蛋白酶体之间的蛋白质降解循环串扰，第一种酶的抑制导致泛素-蛋白酶体系统的下调和癌细胞凋亡的诱导。酰基肽水解酶已被提议作为开发新的潜在抗癌剂的有趣目标。在这里，我们介绍了（1-氨基乙基）膦酸二芳基酯的简单衍生物的合成，即在 N 端和酯环上多样化的丙氨酸的膦酸类似物，作为酰基肽水解酶的抑制剂，并讨论了标题化合物诱导细胞凋亡的能力U937 和 MV-4-11 肿瘤细胞系。