"Emir Khatipov" <khatipovNO at NOuchicago.edu> wrote:
>I would appreciate if someone could help me to solve a rather tricky riddle.
>>When not bound to steroids, steroid receptors (SRs) form complexes with heat
>shock proteins (HSPs) in the cytoplasm. Upon activation with steroids, the
>receptors change conformation, lose the coat of HSPs and penetrate the
>nucleus to activate transcription of target genes.
>>Does anybody know or could come up with an idea how to dissociate SRs from
>HSPs by some physical or chemical stimulation?
>>The reason I am asking is the following. I am trying to develop compounds
>(small molecules, including peptides) that would bind SRs in inactive form.
>I am a priori concerned that due to sterical hindrances those compounds will
>not be able to bind inactive SRs associated with HSPs, so I am trying to
>examine if there is anything known about the ways to dissociation these
>complexes in vivo. I tried to search literature on the subject, but did not
>dig out anything useful so far.
Emir,
The easiest way to dissociate these complexes is to add steroids :-)
No, seriously: add your compound X with a not so potent steroid
(one that has lower affinity for SR). Whether or not your concerns
are justified, doing this should allow you to screen for a potent
inhibitor of steroid translocation into nucleus.
Anything wrong with such approach? Of course you'll get lots
of inhibitor that block other steps, but this _always_ happen
whenever you attempt to do anything in vivo.
DK
