What type of PTM are you looking at? And just to be clear, are you looking at formalin-fixed, parafin-embedded samples? A little more info would help us with your problem. That being said, PBS can often occlude phosphates. As a result, people will often use TBS instead. Similarly, milk can occlude also phosphates, particularly on Tyrosine. As a result, people will often use serum or BSA to block and dilute antibodies. As for fixation itself? Hard to say. Most use formalin-embedded tissues for IHC or fresh frozen. You can also certainly have problems with antigen retrieval of formalin-fixed, parafin-embedded samples.
What type of post transnational modification are you looking for? is it physical, chemical or functional? not clear.And my question for you is how is post-translational modification possible in a fixed tissue?