摘要/Abstract

二酮哌嗪类化合物（DKPs）的特征结构是由两个α-氨基酸通过肽键缩合而成的环二肽（CDPs），稳定的六元环骨架结构使DKPs在药物化学中成为一个重要的药效团，表现出丰富的生物活性.合成可作为药物先导物的DKPs已日益引起人们的关注，其中，开展生物合成研究是拓宽其化学结构多样性的一个有效途径.与早期阐明的非核糖体肽合成酶（NRPSs）生物合成途径不同，环二肽合酶（CDPSs）以氨酰-tRNAs（aa-tRNAs）作为底物合成环二肽，其后修饰过程发生在环二肽形成之后.目前国内外已研究的经CDPS途径合成的二酮哌嗪类化合物报道了6例.对近年来环二肽合酶（CDPSs）生物合成途径相关研究进展进行了综述.
关键词: 二酮哌嗪类化合物, 非核糖体肽合成酶, 环二肽合酶, 生物合成途径
Diketopiperazines (DKPs) are derivatives of cyclodipeptides resulted from the condensation of two α-amino acids. The conformationally constrained six-membered ring makes DKP an attractive pharmacophore in medicinal chemistry, exhibiting a wide range of bioactivities. Recently, there has been increased interests in synthesizing DKPs and biosynthesis is an effective pathway to broaden their structural diversity. Different from non-ribosomal peptide synthetases (NRPSs)-dependent pathways, cyclodipeptide synthases (CDPSs) use aminoacyl-tRNAs (aa-tRNAs) as substrates and the resulting cyclodipeptides are further modified by associated tailoring enzymes to yield the final products. To date, six CDPS-dependent pathways for synthesizing DKPs compounds have been reported. A brief overview of recent progresses on CDPS-dependent DKPs biosynthetic pathway is provided.
Key words: diketopiperazines, non-ribosomal peptide synthetases, cyclodipeptide synthases, biosynthetic pathway


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