title: Investigating the effect of an arterial hypertension drug on the structural properties of plasma protein.
abstract: Propanolol is a betablocker drug used in the treatment of arterial hypertension related diseases. In order to achieve an optimal performance of this drug it is important to consider the possible interactions of propanolol with plasma proteins. In this work, we have used several experimental techniques to characterise the effect of addition of the betablocker propanolol on the properties of bovine plasma fibrinogen (FB). Differential scanning calorimeter (DSC), circular dichroism (CD), dynamic light scattering (DLS), surface tension techniques and atomic force microscopy (AFM) measurements have been combined to carry out a detailed physicochemical and surface characterization of the mixed system. As a result, DSC measurements show that propranolol can play two opposite roles, either acting as a structure stabilizer at low molar concentrations or as a structure destabilizer at higher concentrations, in different domains of fibrinogen. CD measurements have revealed that the effect of propanolol on the secondary structure of fibrinogen depends on the temperature and the drug concentration and the DLS analysis showed evidence for protein aggregation. Interestingly, surface tension measurements provided further evidence of the conformational change induced by propanolol on the secondary structure of FB by importantly increasing the surface tension of the system. Finally, AFM imaging of the fibrinogen system provided direct visualization of the protein structure in the presence of propanolol. Combination of these techniques has produced complementary information on the behavior of the mixed system, providing new insights into the structural properties of proteins with potential medical interest.
authors: Department of Applied Physics University of Santiago de Compostela, Santiago de Compostela, Spain.
authors: Natalia
authors: N
authors: Hassan
authors: Julia
authors: J
authors: Maldonado-Valderrama
authors: A Patrick
authors: AP
authors: Gunning
authors: V J
authors: VJ
authors: Morris
authors: Juan M
authors: JM
authors: Ruso
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002942:Circular Dichroism; D005340:Fibrinogen / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008027:Light; D018625:Microscopy, Atomic Force; D011433:Propranolol / Q000737:chemistry / Q000494:pharmacology*; D017433:Protein Structure, Secondary / Q000187:drug effects*; D012542:Scattering, Radiation; D013499:Surface Properties / Q000187:drug effects; D013500:Surface Tension; D013696:Temperature
chemical_list: D000959:Antihypertensive Agents; D005340:Fibrinogen; D011433:Propranolol