The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
Tubulysins, New Cytostatic Peptides from Myxobacteria Acting on Microtubuli
Production, Isolation, Physico-chemical and Biological Properties
FLORENZ SASSEHEINRICH SIEINMETZJÜRGEN HEILGERHARD HÖFLEHANS REICHENBACH
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2000 Volume 53 Issue 9 Pages 879-885

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Abstract

New cytostatic compounds, tubulysins, were isolated from the culture broth of strains of the myxobacteria Archangium gephyra and Angiococcus disciformis. The compounds are peptides partly consisting of unusual amino acids and are distantly related to the dolastatins. The tubuly sins were not active against bacteria and only little against fungi, but showed high cytostatic activity against mammalian cell lines with IC50 values in the picomolar range. An incubation with 50ng/ml tubulysin A led to a complete disappearance of the microtubuli network of the cells within 24 hours. The more active tubulysin D induced multipolar spindles: At 0.5ng/ml all mitotic cells showed more than four spindle poles.

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