Details
| Original language | English |
|---|---|
| Pages (from-to) | 5269-5278 |
| Number of pages | 10 |
| Journal | Organic and Biomolecular Chemistry |
| Volume | 17 |
| Issue number | 21 |
| Publication status | Published - 7 Jun 2019 |
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.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Chemistry(all)
- Physical and Theoretical Chemistry
- Chemistry(all)
- Organic Chemistry
Sustainable Development Goals
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: Organic and Biomolecular Chemistry, Vol. 17, No. 21, 07.06.2019, p. 5269-5278.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - New geldanamycin derivatives with anti Hsp properties by mutasynthesis
AU - Hermane, Jekaterina
AU - Eichner, Simone
AU - Mancuso, Lena
AU - Schröder, Benjamin
AU - Sasse, Florenz
AU - Zeilinger, Carsten
AU - Kirschning, Andreas
N1 - Funding information: This work was supported by the Deutsche Forschungsgemeinschaft. For funding (Ki397/13-1). We thank Wera Collisi (HZI) for performing the cell proliferation assays. We are indepted to M. Norris for helpful discussions.
PY - 2019/6/7
Y1 - 2019/6/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85066455418&partnerID=8YFLogxK
U2 - 10.1039/c9ob00892f
DO - 10.1039/c9ob00892f
M3 - Article
C2 - 31089638
AN - SCOPUS:85066455418
VL - 17
SP - 5269
EP - 5278
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
SN - 1477-0520
IS - 21
ER -