Experimental and structural testing module to analyze paralogue-specificity and affinity in the Hsp90 inhibitors series.

ABSTRACT: We here describe the first reported comprehensive analysis of Hsp90 paralogue affinity and selectivity in the clinical Hsp90 inhibitor chemotypes. This has been possible through the development of a versatile experimental assay based on a new FP-probe (16a) that we both describe here. The assay can test rapidly and accurately the binding affinity of all major Hsp90 chemotypes and has a testing range that spans low nanomolar to millimolar binding affinities. We couple this assay with a computational analysis that allows for rationalization of paralogue selectivity and defines not only the major binding modes that relay pan-paralogue binding or, conversely, paralogue selectivity, but also identifies molecular characteristics that impart such features. The methods developed here provide a blu

SUBMITTER: Taldone T 

PROVIDER: S-EPMC3985615 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature