Yes, this is tough. We mostly have used DMSO or DMF. You can try detergents, 
but they tend not to be that effective in solubilisation and they might bind to 
your protein rather than the compound you 'd like to bind. If you'd like to be 
adventurous you could try using cyclodextrins  as a solubilisation vehicle. 
These cyclic sugars are often used industrially to get hydrophobic compounds 
soluble in water. If your protein has high enough affinity for your ligand this 
approach may well work. Some pioneering may be required though....

Good luck, Bert
________________________________________
From: CCP4 bulletin board [CCP4BB@JISCMAIL.AC.UK] on behalf of Monica Mittal 
[monica.mitta...@gmail.com]
Sent: Wednesday, October 15, 2014 2:13 PM
To: CCP4BB@JISCMAIL.AC.UK
Subject: [ccp4bb] crystallization with hydrophobic ligands

Dear All

Can anyone give suggestions for handling the solubility problem of
highly hydrophobic compounds, during co-crystallization or inhibition
assays?
The ligands I am using are almost insoluble in aquous medium. In DMSO
or 95% Ethanol, the solubility is higher.
Besides crystallization, this solubility is also a hindrance for
in-vitro or in-vivo assays requiring higher conc. of ligand.

Thanks in advance !
Monica

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