Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
J Pept Sci. 2012 Aug;18(8):500-10. doi: 10.1002/psc.2425. Epub 2012 Jun 29.
As part of an ongoing investigation of filamentous fungi for anticancer leads, an active culture was identified from the Mycosynthetix library (MSX 70741, of the order Hypocreales, Ascomycota). The fungal extract exhibited cytotoxic activity against the H460 (human nonsmall cell lung carcinoma) cell line, and bioactivity-directed fractionation yielded peptaibols 1-12 and harzianums A (13) and B (14). Structure elucidation of 1-12 was facilitated by high-resolution MS/MS using higher-energy collisional dissociation and by high field NMR (950 MHz). The absolute configuration was determined by Marfey's analysis of the individual amino acids; the time required for such analysis was decreased via the development of a 10-min ultra performance liquid chromatography method. The isolated peptaibols (1-12), along with three other peptaibols isolated and elucidated from a different fungus (MSX 57715) of the same order (15-17), were examined for activity in a suite of biological assays, including those for cytotoxic, antibacterial, and anthelmintic activities.
作为对具有抗癌先导作用的丝状真菌进行持续研究的一部分，从 Mycosynthetix 文库（MSX 70741，属于 Hypocreales，子囊菌门）中鉴定出一种活性培养物。真菌提取物对 H460（人非小细胞肺癌）细胞系表现出细胞毒性活性，生物活性导向的分离得到了肽 1-12 和 harzianums A（13）和 B（14）。通过使用更高能量碰撞解离的高分辨率 MS/MS 和高场 NMR（950 MHz），促进了 1-12 的结构阐明。通过对单个氨基酸进行 Marfey 分析确定了绝对构型；通过开发 10 分钟超高效液相色谱方法，缩短了这种分析所需的时间。从同一目（15-17）的另一种真菌（MSX 57715）中分离和阐明的其他三种肽也与分离得到的肽（1-12）一起，在一系列生物测定中进行了活性测试，包括细胞毒性、抗菌和驱虫活性测定。
