Prenylation at the indole ring leads to a significant increase of cytotoxicity of tryptophan-containing cyclic dipeptides
Prenylation at the indole ring leads to a significant increase of cytotoxicity of tryptophan-containing cyclic dipeptides
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DOI：
10.1016/j.bmcl.2012.04.119
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发表时间：
2012-06-15
影响因子：
2.7
通讯作者：
Li, Shu-Ming
中科院分区：
文献类型：
--
作者：
Wollinsky, Beate;Ludwig, Lena;Li, Shu-Ming
使用纯化的重组 FtmPT1 作为催化剂，在二甲基烯丙基二磷酸存在下，将 14 种含色氨酸的环状二肽 1a-14a（包括环 Trp-Pro 和环 Trp-Ala 的所有四种立体异构体）转化为其 C2 规则异戊二烯化衍生物 1b-14b。通过 HPLC 制备型分离酶产物，并通过 NMR 和 MS 分析阐明其结构。使用人白血病 K562 和卵巢癌 A2780 sens 和 A2780 CisR 细胞系测试了异戊二烯化产物及其底物的细胞毒性作用。初步结果清楚地表明，在所有 14 例中，C2 处的异戊二烯化导致所测试的环状二肽的细胞毒性显着增加。第二个氨基酸和环状二肽色氨酸部分的立体化学对测试化合物的细胞毒性影响较小。 (C) 2012 Elsevier Ltd. 保留所有权利。
Fourteen tryptophan-containing cyclic dipeptides 1a-14a, including all four stereoisomers of cyclo-Trp-Pro and cyclo-Trp-Ala, were converted to their C2-regularly prenylated derivatives 1b-14b in the presence of dimethylallyl diphosphate by using the purified recombinant FtmPT1 as catalyst. The enzyme products were isolated on HPLC in preparative scales and their structures were elucidated by NMR and MS analyses.The cytotoxic effects of the prenylated products and their substrates were tested with human leukemia K562 and ovarian cancer A2780 sens and A2780 CisR cell lines. Preliminary results have been clearly shown that prenylation at C2 led to a significant increase of the cytotoxicity of the tested cyclic dipeptides in all the 14 cases. The second amino acid and the stereochemistry of tryptophan moiety of the cyclic dipeptides showed less influence on the cytotoxicity of the tested compounds. (C) 2012 Elsevier Ltd. All rights reserved.