What "different click substrates" are you talking about? As far as I remember There's only one class that's been developed (alkyne azide cycloaddition) -- sharpless really wants norbornene to take off but no one has developed that afaict - and of these only one that can be done in vivo (cyclooctyne + azide); the others require copper catalyst which is not awesome for living cells.

> ... methionine substitute that incorporates into every protein, purify out

This is crazy labor intensive, I feel like if you are at this point in considering using this to understand a biological you have really burned through a lot of simpler, more established, and easy to calibrate techniques.