Energetics of cyclodextrin-induced dissociation of insulin.
The energetics of dissociation of bovine insulin in aqueous solution have been investigated by sensitive dilution microcalorimetry. Cyclodextrins increase dissociation of insulin oligomers in a manner consistent with their interaction with protein side chains. For example, assuming monomer-dimer equilibrium, in the absence of cyclodextrins the calorimetric dilution data (25 degrees C, pH 2.5) indicate a dimer dissociation constant (K(diss)) of about 12 microM and an endothermic dissociation enthalpy (delta H(diss) of +41 kJ mol-1. Addition of methyl-beta-cyclodextrin (up to 200 mM) makes dissociation significantly more endothermic (delta H(diss) = 79 kJ mol-1) and reduces the apparent dimer dissociation constant by more than two orders of magnitude (K(diss) approximately 1.7 mM). Qualitatively similar results are observed with alpha-cyclodextrin and other beta-cyclodextrin derivatives. Cyclodextrin-induced insulin dissociation is also observed at pH 7.4.
Lovatt
M
M
Department of Chemistry, Glasgow University, Scotland, UK.
Cooper
A
A
Camilleri
P
P
D000818:Animals; D002021:Buffers; D002151:Calorimetry; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003505:Cyclodextrins / Q000737:chemistry*; D007328:Insulin / Q000737:chemistry*; D011487:Protein Conformation; D013816:Thermodynamics
D002021:Buffers; D003505:Cyclodextrins; D007328:Insulin