Hi,
In addition to all that's been suggested so far: when I was facing such
problems I always tried the (commercially available) additive screens
(additive kits, whatever they are called nowadays). This means setting
up quite a few crystallisation experiments (you already have conditions
in which crystals grow) and blindly going through the additives. Just in
case a few of them improve the resolution of your crystals, or even
provide another crystal form. I've had plenty of success this way. Of
course the results obtained are not from sessions of hard thinking, what
could be the cause of the problems with the current crystals etc but who
cares? It may be that (for example) a small molecule inserts itself in
the right place to give you the desired result.
Worth trying.
HTH,
Fred.
--
MedChem, 1st F. Medicine, Charles University
BIOCEV, Vestec, Czech Republic
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