Cyclopeptides from the Mushroom Pathogen Fungus Cladobotryum varium
Cyclopeptides from the Mushroom Pathogen Fungus Cladobotryum varium
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来自蘑菇病原体真菌 Cladobotryum varium 的环肽
DOI：
10.1021/acs.jnatprod.0c00980
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发表时间：
2021
影响因子：
5.1
通讯作者：
Igarashi Yasuhiro
中科院分区：
文献类型：
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作者：
Zhou Tao;Katsuragawa Misaki;Xing Tian;Fukaya Keisuke;Okuda Toru;Tokiwa Toshiyuki;Tashiro Etsu;Imoto Masaya;Oku Naoya;Urabe Daisuke;Igarashi Yasuhiro
借助 HPLC-DAD 分析，从 Cladobotryum varium（一种引起蘑菇蜘蛛网病的真菌病原体）的培养液中鉴定出三种具有连续 Phe 残基的新环肽。 Cladoamides A (1) 和 B (2) 在 destruxin 类环状缩酚五肽框架中具有两个连续的 N-甲基苯丙氨酸单元，而 Cladoamide C (3) 在环五肽结构中具有三个连续的 Phe 基序。在这三种环肽中，1 在 10 μg/mL 浓度下显示出有效的自噬诱导活性，与阳性对照雷帕霉素相当。为了测定 1 和 3 中 Ile 残基的绝对构型，在先进 Marfey 方法的分析方案中建立了使用五氟苯基键合固相和甲醇溶剂分离 Ile 和异 Ile 的新条件，从而为需要使用三溶剂混合物洗脱的 C3Marfey 方法提供了方便的替代方法。通过基于DFT的计算和化学合成的NMR化学位移预测，确定了双苯丙氨酸和单苯丙氨酸的序列，证明了非共价相互作用在精确计算具有多个芳环的肽的稳定构象异构体中的重要性。
Three new cyclopeptides with serial Phe residues were identified with the aid of HPLC-DAD analysis, from the culture broth ofCladobotryum varium, a fungal pathogen causing mushroom cobweb disease. Cladoamides A (1) and B (2) have two consecutiveN-methylphenylalanine units in the destruxin class cyclic depsipentapeptide framework, while cladoamide C (3) has a three consecutive Phe motif in a cyclopentapeptide structure. Of these three cyclopeptides,1showed potent autophagy-inducing activity at 10 μg/mL, comparable to a positive control, rapamycin. For the determination of the absolute configurations of the Ile residues in1and3, new conditions for separating Ile andallo-Ile, using a pentafluorophenyl-bonded solid phase and methanolic solvent, were established within the analytical scheme of the advanced Marfey’s method, thus offering a convenient alternative to the C3Marfey’s method, which requires elution with a three-solvent mixture. The sequence of twod-Phe and onel-Phe in3was determined through NMR chemical shift prediction by DFT-based calculations and chemical synthesis, which demonstrated the significance of noncovalent interactions in the accurate calculation of stable conformers for peptides with multiple aromatic rings.