Loading...
New geldanamycin derivatives with anti Hsp properties by mutasynthesis.
Hermane, Jekaterina Eichner, Simone Mancuso, Lena Schröder, Benjamin Sasse, Florenz Zeilinger, Carsten Kirschning, Andreas
Hermane, Jekaterina
Eichner, Simone
Mancuso, Lena
Schröder, Benjamin
Sasse, Florenz
Zeilinger, Carsten
Kirschning, Andreas
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2019-05-29
Submitted date
Files
Loading...
Open Access article
Adobe PDF, 1.12 MB
Other Titles
Abstract
Mutasynthetic supplementation of the AHBA blocked mutant strain of S. hygroscopicus, the geldanamycin producer, with 21 aromatic and heteroaromatic amino acids provided new nonquinoid geldanamycin derivatives. Large scale (5 L) fermentation provided four new derivatives in sufficient quantity for full structural characterisation. Among these, the first thiophene derivative of reblastatin showed strong antiproliferative activity towards several human cancer cell lines. Additionally, inhibitory effects on human heat shock protein Hsp90α and bacterial heat shock protein from H. pylori HpHtpG were observed, revealing strong displacement properties for labelled ATP and demonstrating that the ATP-binding site of Hsps is the target site for the new geldanamycin derivatives.
Citation
Org Biomol Chem. 2019 May 29;17(21):5269-5278. doi: 10.1039/c9ob00892f.
Publisher
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
Description
Series/Report no.
ISSN
1477-0539
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution-NonCommercial-ShareAlike 4.0 International