PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 33Citation - Scopus: 36Epr Studies of Intermolecular Interactions and Competitive Binding of Drugs in a Drug-Bsa Binding Model(Royal Society of Chemistry, 2016) Akdoğan, Yaşar; Emrullahoğlu, Mustafa; Tatlıdil, Diğdem; Üçüncü, Muhammed; Çakan Akdoğan, GülçinUnderstanding intermolecular interactions between drugs and proteins is very important in drug delivery studies. Here, we studied different binding interactions between salicylic acid and bovine serum albumin (BSA) using electron paramagnetic resonance (EPR) spectroscopy. Salicylic acid was labeled with a stable radical (spin label) in order to monitor its mobilized (free) or immobilized (bound to BSA) states. In addition to spin labeled salicylic acid (SL-salicylic acid), its derivatives including SL-benzoic acid, SL-phenol, SL-benzene, SL-cyclohexane and SL-hexane were synthesized to reveal the effects of various drug binding interactions. EPR results of these SL-molecules showed that hydrophobic interaction is the main driving force. Whereas each of the two functional groups (-COOH and -OH) on the benzene ring has a minute but detectable effect on the drug-protein complex formation. In order to investigate the effect of electrostatic interaction on drug binding, cationic BSA (cBSA) was synthesized, altering the negative net charge of BSA to positive. The salicylic acid loading capacity of cBSA is significantly higher compared to that of BSA, indicating the importance of electrostatic interaction in drug binding. Moreover, the competitive binding properties of salicylic acid, ibuprofen and aspirin to BSA were studied. The combined EPR results of SL-salicylic acid/ibuprofen and SL-ibuprofen/salicylic acid showed that ibuprofen is able to replace up to ∼83% of bound SL-salicylic acid, and salicylic acid can replace only ∼14% of the bound SL-ibuprofen. This indicates that ∼97% of all salicylic acid and ibuprofen binding sites are shared. On the other hand, aspirin replaces only ∼23% of bound SL-salicylic acid, and salicylic acid replaces ∼50% of bound SL-aspirin, indicating that ∼73% of all salicylic acid and aspirin binding sites are shared. These results show that EPR spectroscopy in combination with the spin labeling technique is a very powerful method to investigate drug binding dynamics in detail.Article Citation - WoS: 24Citation - Scopus: 27Physiological Concentrations of Albumin Favor Drug Binding(Royal Society of Chemistry, 2015) Tatlıdil, Diğdem; Üçüncü, Muhammed; Akdoğan, YaşarThe ability to track drug binding and release makes electron paramagnetic resonance (EPR) spectroscopy well suited for drug delivery studies. Using the continuous wave (cw) EPR technique to extract information about the dynamics of the spin labeled drugs we can simultaneously determine the bound and unbound drugs. Here, spin labeled salicylic acid (SLSA) binding to and release from bovine serum albumin (BSA) is investigated, as a model for drug-transport protein interaction. We studied SLSA-BSA binding in a wide concentration range and found that the stoichiometry of the drug-protein increases significantly when the physiological range of BSA concentration is reached. Our EPR results explicitly reveal that up to ∼7 SLSA can bind to one albumin at the physiological concentration, whereas at lower BSA concentrations (<0.125 mM) the SLSA-BSA stoichiometry is maximum 2. Moreover, we studied drug release and showed that the ratio of bound to unbound SLSA concentrations remains relatively stable during dialysis. This indicates that the binding equilibrium of SLSA is not altered through the process of dialysis. This study demonstrates that cw EPR spectroscopy in combination with spin labeled drugs is an effective technique for binding and release studies and stoichiometric analysis of drug-protein interactions.