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In vitro activities and postantifungal effects of the potent dolastatin 10 derivative auristatin PHE.强效多拉司他汀10衍生物奥瑞他汀PHE的体外活性及抗真菌后效应。
Antimicrob Agents Chemother. 2001 Dec;45(12):3580-4. doi: 10.1128/AAC.45.12.3580-3584.2001.
2
Microtubules and actin cytoskeleton in Cryptococcus neoformans compared with ascomycetous budding and fission yeasts.新型隐球菌中微管和肌动蛋白细胞骨架与子囊芽殖酵母和裂殖酵母的比较
Eur J Cell Biol. 2001 Apr;80(4):303-11. doi: 10.1078/0171-9335-00157.
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Microtubule interactions with the cell cortex causing nuclear movements in Saccharomyces cerevisiae.微管与细胞皮层的相互作用导致酿酒酵母中的核运动。
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Specific activities of dolastatin 10 and peptide derivatives against Cryptococcus neoformans.多拉司他汀10及其肽衍生物对新型隐球菌的比活性。
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[Three-dimensional reconstruction of mitotic cells of Cryptococcus neoformans based on serial section electron microscopy].基于连续切片电子显微镜的新型隐球菌有丝分裂细胞的三维重建
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Antineoplastic agents 365. Dolastatin 10 SAR probes.抗肿瘤药365. 多拉司他汀10的构效关系探针。
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Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group.获得性免疫缺陷综合征相关隐球菌性脑膜炎的治疗。美国国立过敏和传染病研究所真菌病研究组及艾滋病临床试验组。
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10
beta-Tubulin genes and the basis for benzimidazole sensitivity of the opportunistic fungus Cryptococcus neoformans.β-微管蛋白基因与机会性真菌新型隐球菌对苯并咪唑敏感性的基础。
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奥瑞他汀PHE对新型隐球菌微管完整性和核定位的影响。

Effect of auristatin PHE on microtubule integrity and nuclear localization in Cryptococcus neoformans.

作者信息

Woyke Tanja, Roberson Robert W, Pettit George R, Winkelmann Günther, Pettit Robin K

机构信息

Cancer Research Institute, Arizona State University, Tempe 85287, USA.

出版信息

Antimicrob Agents Chemother. 2002 Dec;46(12):3802-8. doi: 10.1128/AAC.46.12.3802-3808.2002.

DOI:10.1128/AAC.46.12.3802-3808.2002
PMID:12435680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC132747/
Abstract

The mechanism of action of the fungicidal peptide auristatin PHE was investigated in Cryptococcus neoformans. Since auristatin PHE causes budding arrest in C. neoformans (T. Woyke, G. R. Pettit, G. Winkelmann, and R. K. Pettit, Antimicrob. Agents Chemother. 45:3580-3584, 2001), microtubule integrity and nuclear localization in auristatin PHE-treated cells were examined. Iterative deconvolution in conjunction with an optimized C. neoformans microtubule immunolabeling procedure enabled detailed visualization of the microtubule cytoskeleton in auristatin PHE-treated C. neoformans. The effect of auristatin PHE on C. neoformans microtubule organization was compared with that of the tubulin-binding agent nocodazole. Both drugs produced complete disruption first of cytoplasmic and then of spindle microtubules in a time- and concentration-dependent manner. Sub-MICs of auristatin PHE caused complete microtubule disruption within 4.5 h, while 1.5 times the nocodazole MIC was required for the same effect. For both drugs, disruption of microtubules was accompanied by blockage of nuclear migration and of nuclear and cellular division, resulting in cells arrested in a uninucleate, large-budded stage. Nocodazole and the linear peptide auristatin PHE are remarkably different in structure and spectrum of activity, yet on the cellular level, they have similar effects.

摘要

研究了杀真菌肽奥瑞他汀PHE在新型隐球菌中的作用机制。由于奥瑞他汀PHE会导致新型隐球菌出芽停滞（T. Woyke、G. R. Pettit、G. Winkelmann和R. K. Pettit，《抗菌剂与化疗》，45:3580 - 3584，2001年），因此检测了经奥瑞他汀PHE处理的细胞中的微管完整性和核定位。迭代反卷积结合优化的新型隐球菌微管免疫标记程序，能够详细观察经奥瑞他汀PHE处理的新型隐球菌中的微管细胞骨架。将奥瑞他汀PHE对新型隐球菌微管组织的影响与微管蛋白结合剂诺考达唑的影响进行了比较。两种药物均以时间和浓度依赖性方式首先导致细胞质微管，然后是纺锤体微管的完全破坏。奥瑞他汀PHE的亚最小抑菌浓度在4.5小时内导致微管完全破坏，而达到相同效果需要1.5倍诺考达唑的最小抑菌浓度。对于这两种药物，微管的破坏都伴随着核迁移以及核和细胞分裂的阻滞，导致细胞停滞在单核、大芽阶段。诺考达唑和线性肽奥瑞他汀PHE在结构和活性谱上有显著差异，但在细胞水平上，它们具有相似的作用。