I think it is simply because the buffers already have EDTA, so you don't need extra EDTA in the protease inhibitor cocktail. Alternatively, many labs report a protocol that "works" with the way they do--even as it might not sound too logical. For example, in the early TAP-tag purification protocols, it was recommended to have some imidazole there, whereas the protocol did NOT use Ni-NTA. No explanations for these irritants! If it works, you don't worry.

That said, I guess you would be ok to use your +EDTA protease inhibitor tablets.

Most people prefer EDTA-free tablets. This is because, many people use nucleases to digest the cell lysate. For example, in ChIP, 3C-based assays; or just to reduce the lysate viscosity. At the same time, proteases need to be kept under control during nuclease digestion. This can be achieved by using EDTA-free protease-inhibitors and supplementing the lysate with the required divalent cation (CaCl2 or MgCl2). You can't add Ca/Mg to your lysate if it already has EDTA!

So, don't worry and use your +EDTA tablets, and I am positive that you would be fine!

Hi there,

The main purpose of EDTA free cocktail is that it is suitable for both situations whereas the one with EDTA can only be used in the context of the presence of EDTA. At first EDTA free cocktail was thought for instance for NiNTA purification protocol.

I agree in using regular protease tablets if you have EDTA in your buffers.