RE: Drug studies

From: Calman Prussin (CPRUSSIN@atlas.niaid.nih.gov)
Date: Wed May 28 1997 - 20:50:08 EST


I would be very surprised if this fixation approach worked.

Proteins can be fixed inside a cell because they can be 1.) 
cross-linked or 2.) made insoluble by the fixation process; this 
latter process has been termed coagulative fixation and is due to 
partial denaturation. A small organic molecule like a drug, is 
unlikely to be able to be cross linked by PFA and will not denature as 
a protein would. If you got lucky and by chance did have a drug that 
had a site that was amenable to cross linking, it would likely disrupt 
the Ab binding site. Proteins work in part because they are large 
molecules and you can fiddle with one part without disrupting the Ab 
binding site.

Call me Mr. Optimist!

Calman Prussin
Laboratory of Allergic Diseases
NIAID/ National Institutes of Health

----------
From: 	Richard K. Meister
Sent: 	Wednesday, May 28, 1997 3:20 PM
To: cyto-inbox
Subject: 	Drug studies


Hi, everyone:

I have an investigator who wants to look at intracellular distribution 
of a
drug using confocal laser scanning microscopy.  The drug is not 
fluorescent,
so he has a monoclonal antibody (FITC conjugate) to the drug.  Our 
question
is, during permeablization to allow the antibody into the cells, what 
is the
best way to prevent the drug from leaching out of the cells?  I 
suppose a
pre-permeablization paraformaldehyde fixation step would be helpful, 
but I
would like to hear from anyone who has done such drug studies and 
knows if
this is an effective approach.

Thanks in advance.



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