So I've never actually tried this proposed extension to the idea, but: I (and many others) have gotten small hydrophobics (toluene, iodobenzene etc.) into proteins, and these things typically have very small partition coefficients, and they aren't horribly volatile (that's why I am a little partial to iodobenzene).
Why not saturate a small solution of your small molecule in iodobenzene and just add a few microliters on top; if the binding is tight enough you can pull it through and not bug your protein with a denaturing co-solvent. I've noticed that the iodobenzene does largely disappear overnight (in hanging drop), I don't know if this is because of evaporation or the iodobenzene just "falls" into the reservoir. Maybe stick to sitting drop. -----Original Message----- From: CCP4 bulletin board on behalf of Green, Todd Sent: Mon 1/22/2007 12:40 PM To: [email protected] Subject: crystal friendly solvents that are useful for dissolving hydrophobic small molecules? Hello All, I am trying to soak some crystals with a small molecule that is quite hydrophobic. I am having trouble with solubilty of the small molecule. It will dissolve up to about 1 mM in 100 % DMSO, but precipitates at concentrations of less than 15 micromolar when the DMSO concentration is below 20 percent in my crystal growth solutions(which are peg 4k, low pH, low salt). Can anyone suggest solvents other than DMSO which might help dissolve the inhibitor and might be somewhat friendly to my crystals. Thanks in advance- Todd Green
