Pitfalls in the use of carboxylic acid anhydrides for structural studies of nucleoprotein particles

During modification of protein amino groups with carboxylic acid anhydrides, these reagents cause a fall in pH, which can be prevented by addition of base. Although unmodified nucleosomal particles are not affected by the local transient changes in pH induced by the base (NaOH) added to prevent a fall in pH during modification, the nucleosomal particles modified by acetic anhydride are dissociated, with release of single-stranded DNA.