Valence and anion binding of bovine ribonuclease A between pH 6 and 8

Establishing a Link Between Amino Acid Sequences and Self-Associating and Viscoelastic Behavior of Two Closely Related Monoclonal Antibodies

“…Previously, it has been shown that the theoretically computed charge values have been in good agreement for many globular proteins (40,41), whereas for MAbs the experimental charge was observed to be 15-20 units below the theoretically estimated value (personal communication: unpublished data from the laboratory of Dr. Thomas M. Laue, University of New Hampshire). Additionally, the presence of counter-ion and its possible binding with macro-ion may alter the effective molecular charge, which is not accounted for in theoretical calculations (40). At any rate, both theoretical and experimental results indicated a change in effective charge on the molecules following mutations.…”

Developability Assessment During the Selection of Novel Therapeutic Antibodies

“…). Remaining discrepancies between predicted and observed net charge may be explained by protein interactions with salt ions (see above), which are notoriously difficult to capture in silico , so that only a measurement of effective net charge is capable of providing exact results . Besides net charge, the distribution of charge across the molecule can influence the solution behavior of a protein.…”

Stability of Protein Pharmaceuticals: An Update

“…For example, sulfate appears to bind to endostatin (429) and ribonuclease (430). Ribonuclease has also been shown to bind two moles of chloride ion, resulting in significant structural stabilization (∼2-3 kJ/mol) (431). Stabilization of HSA has been observed from binding chloride (432) and carboxylates, such as formate and acetate (433).…”