Hi Leon, I can recommend the Cryosol kit from Molecular Dimensions: https://moleculardimensions.com/en/product/MD1-90
https://pmc.ncbi.nlm.nih.gov/articles/PMC5466044/ The use of multi-component solvent mixtures can dramatically boost aqueous solubility of otherwise immiscible ligands. I have had the greatest success with SM1 and SM4. Key points: 1. You need to have a minimum of 40% v/v, and sometimes 50% is better, of the solubilising cryo-mixture. 2. Crystals are often soluble in well-solution + 40-50% v/v of cryomix. 3. So you need to make higher concentration of precipitant such that dilution with the cryo-mixture gives you at least the same concentration as in the well – going a few % higher is also often advantageous. 4. If your crystals grew in a salt based system then I would explore moving them into a PEG environment as this will again help with ligand solubiity. 5. If your crystals grew from high MW PEG then explore transferring them into a higher concentration of lower MW PEG or a PEG smear including low MW species as this will again usually increase ligand solubility Cheers, Charlie. From: CCP4 bulletin board <[email protected]> On Behalf Of Maria Jose Sanchez Barrena Sent: 13 May 2026 08:00 To: [email protected] Subject: Re: [ccp4bb] Fragment soaking protein crystals with small molecules WARNING: This message was sent by an external party. Report suspicious messages via the “Report Phishing” button in Outlook. Hi Leon:We have crystalized several protein-ligand complexes by solubilizing the compounds in ethanol. I would try solubility in such solvent.I you need DMSO, test how much your protein stands DMSO and you could also add your compound (solubilized in 100% DMSO) to your protein.Good luck,Maria ------ i This message needs your attention * This is their first email to your company. Powered by Mimecast CGBANNERINDICATOR Hi Leon: We have crystalized several protein-ligand complexes by solubilizing the compounds in ethanol. I would try solubility in such solvent. I you need DMSO, test how much your protein stands DMSO and you could also add your compound (solubilized in 100% DMSO) to your protein. Good luck, Maria -------------------- María José Sánchez-Barrena Department of Crystallography and Structural Biology Instituto de Química Física “Blas Cabrera”. CSIC. Calle de Serrano 119. 28006 Madrid Tel: 0034 915619400 ext. 442058 http://www.xtal.iqf.csic.es/grupo/xmjose/<http://www.xtal.iqfr.csic.es/grupo/xmjose/> @sanchez_barrena El 12 may 2026, a las 18:16, Giang, Leon (MU-Student) <[email protected]<mailto:[email protected]>> escribió: Hello everyone, I am looking for advice on my fragment soaking protocol. Recently, I obtained a crystal structure of a small molecule within my protein. These compounds are insoluble in aqueous solution so I've been preparing aliquots of the compound at known concentrations in 100% DMSO. I aliquot the compounds onto pedestal of sitting drop trays then wait for the DMSO to evaporate before adding my cryo-protectant solution and pre-grown protein crystals. I am trying to reproduce my results with different concentrations of compound but have to wait a long time for the DMSO to evaporate. I am looking for advice on how to speed up the DMSO evaporation. Thanks, Leon ________________________________ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1<https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1> ________________________________ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1<https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1> ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
