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New, Non‐quinone Fluorogeldanamycin Derivatives Strongly Inhibit Hsp90
Author(s) -
Hermane Jekaterina,
Bułyszko Ilona,
Eichner Simone,
Sasse Florenz,
Collisi Wera,
Poso Antti,
Schax Emilia,
Walter JohannaGabriela,
Scheper Thomas,
Kock Klaus,
Herrmann Christian,
Aliuos Pooyan,
Reuter Günter,
Zeilinger Carsten,
Kirschning Andreas
Publication year - 2015
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402375
Subject(s) - geldanamycin , hsp90 , streptomyces hygroscopicus , quinone , heat shock protein , chemistry , mutant , hsp90 inhibitor , biochemistry , stereochemistry , streptomyces , biology , genetics , bacteria , gene
Streptomyces hygroscopicus is a natural producer of geldanamycin. Mutasynthetic supplementation of an AHBA‐blocked mutant with all possible monofluoro 3‐aminobenzoic acids provided new fluorogeldanamycins. These showed strong antiproliferative activity and inhibitory effects on human heat shock protein Hsp90. Binding to Hsp90 in the low nanomolar range was determined from molecular modelling, AFM analysis and by calorimetric studies.