Mechanisms of fibrinogen-acebutolol interactions: Insights from DSC, CD and LS.
The complex formed due to the interaction of the amphiphilic betablocker acebutolol with fibrinogen in a buffer solution (50mN glycine, pH of 8.5) has been investigated using a multipronged physicochemical approach. Differential scanning calorimetry measurements of the complexes have shown no reversibility of thermal denaturation as indicated by the three observed peaks and the opposite role that acebutolol plays in the folding different domains of the fibrinogen molecule and the stability of such domains. While circular dichroism measurements have revealed that interaction of acebutolol with fibrinogen affects the protein secondary structure to a different extent depending on the temperature and drug concentration, dynamic light scattering analysis showed evidence for protein aggregation mainly to tetramers and dimers.
Soft Matter and Molecular Biophysics Group, Department of Applied Physics University of Santiago de Compostela, Campus Vida s/n, 15782, Santiago de Compostela, Spain.
Natalia
N
Hassan
Juan M
JM
Ruso
P
P
Somasundaran
D000070:Acebutolol / Q000737:chemistry*; D000818:Animals; D002021:Buffers; D002152:Calorimetry, Differential Scanning / Q000379:methods*; D002417:Cattle; D002627:Chemistry, Physical / Q000379:methods; D002942:Circular Dichroism / Q000379:methods*; D019281:Dimerization; D005340:Fibrinogen / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008027:Light; D008956:Models, Chemical; D017510:Protein Folding; D012542:Scattering, Radiation
D002021:Buffers; D000070:Acebutolol; D005340:Fibrinogen; D005998:Glycine