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