ABSTRACT
The dissociation rate and capability of IN to change from the hexamers through dimers to the biologically active monomers is a property relevant for IN therapy because it controls the rate of action of injected IN. It can be modulated through different meth ods: by controlling pH, protein concentration, metal ion content, ionic strength, and solvent composition [38,42]. Alternatively, the self-association can be reduced by the introduction of charge repulsions into the monomer-monomer interface [53] by amino acid substitution or by the removal of some of the amino acid residues responsible for the dimerization. Thanks to their low molecular weight, many of these stable mono meric mutants have been the subject of structural studies in solution, through NMR. However, most of these analogues do not bind zinc [54-63].