I have tried different ways of co-IP to detect the interaction of a couple of small leucine-rich proteoglycan (SLRP) family members with ErbB family members, but I have failed. It seems that my lysis buffer for co-IP is too stringent (although I use mild detergents like NP-40) and dissociates any interaction made by these proteins. I also keep getting a dirty pre-cleared fraction, i.e. my IgG binds non-specificlly to these proteoglycans. I was wondering if anybody has a good protocol to co-IP proteoglycns? I do not have that much of experience with them and I appreciate any feedback or help.