Those of you who are into CRISPR will likely have heard for SCR7. It’s a compound added to the system that seems to enhance its efficiency and specificity, presumably through its inhibition of DNA ligase IV. That’s all fine – the mechanism makes sense, and making CRISPR more selective is a worthy goal that any number of labs are working on. That SCR7 structure is deeply unappealing, to be sure (two Schiff bases!), although all it has to do is hang around enough in vitro to do its thing. But there seems to be a problem with SCR7 itself.
That’s what the people at Tocris are saying. Tocris is one of the larger (and definitely one of the more reliable) companies that sell inhibitors, ligands, and preclinical compounds for all sorts of targets. They’ve noticed that the material being sold by other vendors does not seem to match the reported structure. Instead, what’s out there seems to be the related pyrazine compound (at right). It appears that the pyrazine is actually the active compound in the CRISPR system, which makes you wonder if it’s the active compound in the original 2012 paper on its use as a ligase inhibitor as well.
This also brings up thoughts of quality control, since the mass of the pyrazine compound is two hydrogens off that of the original structure (which should be immediately apparent in mass spec) and even more apparent in an NMR (those imine protons should be very distinctive). One might get the impression that there are some suppliers who didn’t bother looking at either of those very closely, or who just took what they got from some other source and ran with it under their own label. Worth keeping in mind next time you’re purchasing some tool compound. . .