This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Woyke, T.
Right arrow Articles by Pettit, R. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Woyke, T.
Right arrow Articles by Pettit, R. K.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, December 2001, p. 3580-3584, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3580-3584.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

In Vitro Activities and Postantifungal Effects of the Potent Dolastatin 10 Derivative Auristatin PHE

Tanja Woyke,1,2 George R. Pettit,1,3 Günther Winkelmann,2 and Robin K. Pettit1,4,*

Cancer Research Institute1 and Departments of Microbiology4 and Chemistry and Biochemistry,3 Arizona State University, Tempe, Arizona 85287-2404, and Eberhard Karls University Tübingen, 72076 Tübingen, Germany2

Received 17 November 2000/Returned for modification 18 May 2001/Accepted 24 July 2001

The pentapeptide dolavaline-valine-dolaisoleuine-dolaproine-phenylalanine-methyl ester (auristatin PHE) is a derivative of the anticancer drug dolastatin 10 (dolavaline-valine-dolaisoleuine-dolaproine-dolaphenine). Broth microdilution assays with a wide variety of yeast and filamentous fungal species demonstrated the specificity of auristatin PHE for Cryptococcus neoformans and several species of Trichosporon. The duration of the postantifungal effect (PAFE) for C. neoformans was determined for exposure times ranging from 30 min to 2 h. For the derivative, a PAFE was detectable after 45 min of exposure. The effect plateaued after 1 h of exposure, with a PAFE of approximately 6.5 h at four or eight times the auristatin PHE MIC. In contrast, there was no measurable PAFE after 1 h of exposure to dolastatin 10. Human serum greatly prolonged the PAFE of auristatin PHE at eight times the MIC. Auristatin PHE arrested C. neoformans in the budding stage, possibly due to a tubulin-inhibitory action. Auristatin PHE has potential as a narrow-spectrum fungicidal agent and as a probe that can be used to study cryptococcal cell division.

* Corresponding author. Mailing address: Cancer Research Institute, Arizona State University, Tempe, AZ 85287-2404. Phone: (480) 965-4907. Fax: (480) 965-8558. E-mail: pettitr{at}asu.edu.

Antimicrobial Agents and Chemotherapy, December 2001, p. 3580-3584, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3580-3584.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Woyke, T., Berens, M. E., Hoelzinger, D. B., Pettit, G. R., Winkelmann, G., Pettit, R. K. (2004). Differential Gene Expression in Auristatin PHE-Treated Cryptococcus neoformans. Antimicrob. Agents Chemother. 48: 561-567 [Abstract] [Full Text]  
  • Woyke, T., Roberson, R. W., Pettit, G. R., Winkelmann, G., Pettit, R. K. (2002). Effect of Auristatin PHE on Microtubule Integrity and Nuclear Localization in Cryptococcus neoformans. Antimicrob. Agents Chemother. 46: 3802-3808 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»