Knocking off HSPs. How?

Artem Evdokimov AEVDOKIMOZ at cinci.rr.com
Thu May 9 20:18:50 EST 2002


> 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?

Apart from the ideas suggested here by others - you could consider
denaturation & renaturation. Pain in the neck, though. High concentrations
of betains and related compounds may work without completely denaturing the
target. Expression outside the cell (in suitable system) may work too. I am
still not sure if you seek to obtain competent pure receptor or you need to
'denude' the receptor while it's in the cell. :)

> (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

Out of curiosity - if your target protein is always coated by HSP's in the
cytoplasm, then why do you think that the naked protein is a good target for
your proto-therapeutic ? After all, in the cell it will most likely live in
complex with HSP's or with the steroids most of the time. Would it be easier
to target the steroid-bound receptor, on its way to the nucleus or even the
HSP-protein complex ?

Good luck,

A.G.E.





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