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].