Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 18Citation - Scopus: 20A Simple Desolvation Method for Production of Cationic Albumin Nanoparticles With Improved Drug Loading and Cell Uptake(Editions de Sante, 2020) Sözer, Sümeyra Çiğdem; Özmen Egesoy, Tuğçe; Başol, Merve; Çakan Akdoğan, Gülçin; Akdoğan, YaşarThe transport protein albumin has been used as a drug nanocarrier for a long time due to its versatility. Albumin is negatively charged at physiological conditions limiting its anionic drug loading capacity. However, loading of anionic drugs in the albumin nanoparticles (NPs), can be facilitated by albumin cationization. Here, we postulate a simple desolvation method for preparation of cationic albumin NPs with improved anionic drug loading. First, bovine serum albumin was cationized with ethylenediamine. Next, salicylic acid (SA) was added to the cationic bovine serum albumin (cBSA) solution prior to the desolvation. Among different desolvating agents tested, acetonitrile allowed the highest nanoparticle formation yield. The SEM analyses showed that the average size of cBSA NPs decreased from ~200 nm to ~100 nm upon SA loading. Moreover, the drug loading capacity of cBSA NPs was found to increase ~2 fold, and drug release was slower compared to BSA NPs. Finally, a significant increase in cellular uptake of cBSA NPs compared to that of native BSA NPs showed the potential for improved drug delivery. © 2020 Elsevier B.V.Article Citation - WoS: 10Citation - Scopus: 12The Effect of Dopa Hydroxyl Groups on Wet Adhesion To Polystyrene Surface: an Experimental and Theoretical Study(Elsevier, 2020) Yıldız, Remziye; Özen, Sercan; Şahin, Hasan; Akdoğan, YaşarMussels wet adhesive performance has been arousing curiosity for a long time. It is found that 3,4-dihydroxyphenylalanine (DOPA) is responsible for adhesive properties of mussels. Despite a large body of research characterizing the interactions DOPA with hydrophilic surfaces, relatively few works have addressed the mechanism of interactions with hydrophobic surfaces. The benzene ring of DOPA is the main attributor to the adhesion on hydrophobic polystyrene (PS) surface. However, here we showed that two hydroxyl groups of catechol have also effects on wet adhesion. We studied wet adhesive properties of DOPA, tyrosine and phenylalanine functionalized PEG polymers, PEG-(N-Boc-L-DOPA)(4), PEG-(N-Boc-L-Tyrosine)(4), PEG-(N-Boc-L-Phenylalanine)(4), on spin labeled PS nanobeads (SL-PS) by electron paramagnetic resonance (EPR) spectroscopy. Surface coverage ratio of SL-PS upon additions of PEG-(N-Boc-L-DOPA)(4), PEG-(N-Boc-L-Tyrosine)(4) and PEG-(N-Boc-L-Phenylalanine)(4) showed that SL-PS was covered with 70%, 50% and 0%, respectively. This showed that spontaneous wet adhesion on PS increases with the number of amino acids hydroxyl groups. This is also supported with the density functional theory (DFT) energy calculations and ab-initio molecular dynamics (AIMD) simulations. In water, interactions between water molecules and hydroxyl groups on the catechol induce catechol adhesion via 7C-7C stacking between the catechol and double styrene rings which were already tilted out with water.Article Citation - WoS: 17Citation - Scopus: 18Development of an Ionic Liquid Based Method for the Preparation of Albumin Nanoparticles(John Wiley and Sons Inc., 2018) Demirkurt, Begüm; Akdoğan, YaşarAlbumin based nanocarriers have been widely used in drug delivery studies. Here, we developed a water-in-ionic liquid (IL) emulsion-like method to prepare bovine serum albumin (BSA) nanoparticles as alternative to the traditional organic solvents containing techniques. Conformational changes of albumin induced by the imidazolium based ILs at the water-IL interface triggers the BSA nanoparticle formation. The albumin nanoparticle formation are dependent on the experimental parameters and the hydophobicity of the IL. At pH 9.0, using 1.3%wt of BSA in water/1-butyl-3-methyl imidazolium tetrafluoroborate (BmimBF4) (50/50 mol%) and TX-100/butanol surfactant mixture yields uniformly distributed 200 nm average sized BSA nanoparticles. Different than BmimBF4, using a more hydrophilic IL, EmimBF4 yielded albumin aggregates. Instead, using a more hydrophobic IL, HmimBF4 produced albumin nanoparticles but a non-uniform size distribution was obtained. These results indicate that the ionic liquids called green and designer solvents can be also used to synthesize albumin nanoparticles.Conference Object Citation - Scopus: 1Spontaneous Adhesion of Dopa and Tryptophan Functionalized Peg To Polystyrene Nanobeads: an Epr Study(Trans Tech Publications, 2018) Göksel, Yaman; Kırpat, İklima; Akdoğan, YaşarWet adhesion is achieved by mussels so naturally. Their adhesion mechanism has inspired scientists to obtain wet adhesives for a long time. The amino acid 3,4-dihydroxyphenylalanine (DOPA) produced by mussels adheres to different types of surfaces and also contributes to cohesive interactions. Here, we showed the spontaneous adhesion of DOPA functionalized four armed poly(ethylene glycol) (PEG) polymer to spin labeled polystyrene (SL-PS) nanosurfaces by electron paramagnetic resonance (EPR) spectroscopy. In addition to DOPA, adhesion property of another amino acid of tryptophan (Trp) was studied. Trp attached four armed PEG polymers did not adhere to the surface of SL-PS in the force free condition. However, two armed DOPA and two armed Trp functionalized PEG adhere to the PS.Article Citation - WoS: 5Citation - Scopus: 6Determination of Force-Free Wet Adhesion of Mussel-Inspired Polymers To Spin Labeled Surface(Elsevier, 2017) Kırpat, İklima; Göksel, Yaman; Karakuş, Erman; Emrullahoğlu, Mustafa; Akdoğan, YaşarHydration repulsive forces oppose the adhesive interactions, especially in the force-free conditions. Here, we studied spontaneous wet adhesion of 3,4-dihydroxyphenylalanine (DOPA) functionalized poly(ethylene glycol) (PEG) polymers inspired by marine mussels. Using electron paramagnetic resonance (EPR) spectroscopy, we can monitor spontaneous adhesion of DOPA containing polymer to suspended spin labeled hydrophobic polystyrene nanobeads at molecular level. The surface coverage up to 82% is obtained from EPR measurements. However, in the force-free condition, EPR measurements do not show any detectable DOPA based adhesion to hydrophilic silica nanobead.Article Citation - WoS: 13Citation - Scopus: 16Experimental Modeling of Silicate-Based Geothermal Deposits(Elsevier Ltd., 2017) Çelik, Aslı; Topçu, Gökhan; Baba, Alper; Akdoğan, Yaşar; Şentürk, Ufuk; Demir, Mustafa MuammerScaling by metal silicates represents a major obstacle for geothermal systems. A composition that enables the fabrication of artificial deposits is necessary for the rapid testing of potential inhibitors. In this work, artificial deposits were synthesized by employing experimental conditions similar to those in the Tuzla Geothermal Field in Turkey. Although refluxing enabled the formation of a precipitate that was similar to naturally formed deposits in color and texture, their elemental composition and morphology showed a mismatch. An autoclave enabled the production of a precipitate that more closely resembled naturally formed deposits in color, texture, elemental composition, and structure.Article Citation - WoS: 66Citation - Scopus: 71Signature of an Aggregation-Prone Conformation of Tau(Nature Publishing Group, 2017) Eschmann, Neil A.; Georgieva, Elka R.; Ganguly, Pritam; Borbat, Peter P.; Rappaport, Maxime D.; Akdoğan, Yaşar; Freed, Jack H.; Shea, Joan-Emma; Han, SongiThe self-assembly of the microtubule associated tau protein into fibrillar cell inclusions is linked to a number of devastating neurodegenerative disorders collectively known as tauopathies. The mechanism by which tau self-assembles into pathological entities is a matter of much debate, largely due to the lack of direct experimental insights into the earliest stages of aggregation. We present pulsed double electron-electron resonance measurements of two key fibril-forming regions of tau, PHF6 and PHF6∗, in transient as aggregation happens. By monitoring the end-to-end distance distribution of these segments as a function of aggregation time, we show that the PHF6 (∗) regions dramatically extend to distances commensurate with extended β-strand structures within the earliest stages of aggregation, well before fibril formation. Combined with simulations, our experiments show that the extended β-strand conformational state of PHF6 (∗) is readily populated under aggregating conditions, constituting a defining signature of aggregation-prone tau, and as such, a possible target for therapeutic interventions.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.Article Citation - WoS: 58Citation - Scopus: 86Intrinsic Surface-Drying Properties of Bioadhesive Proteins(John Wiley and Sons Inc., 2014) Akdoğan, Yaşar; Wei, Wei; Huang, Kuo-Ying; Kageyama, Yoshiyuki; Danner, Eric W.; Miller, Dusty R.; Martinez Rodriguez, Nadine R.; Waite, J. Herbert; Han, SongiSessile marine mussels must "dry" underwater surfaces before adhering to them. Synthetic adhesives have yet to overcome this fundamental challenge. Previous studies of bioinspired adhesion have largely been performed under applied compressive forces, but such studies are poor predictors of the ability of an adhesive to spontaneously penetrate surface hydration layers. In a force-free approach to measuring molecular-level interaction through surface-water diffusivity, different mussel foot proteins were found to have different abilities to evict hydration layers from surfaces - a necessary step for adsorption and adhesion. It was anticipated that DOPA would mediate dehydration owing to its efficacy in bioinspired wet adhesion. Instead, hydrophobic side chains were found to be a critical component for protein-surface intimacy. This direct measurement of interfacial water dynamics during force-free adsorptive interactions at solid surfaces offers guidance for the engineering of wet adhesives and coatings. Home and dry underwater: Repulsive hydration forces hinder wet adhesion in the absence of applied external forces. The direct measurement of hydration-water dynamics by NMR relaxometry at 10 GHz revealed that the most hydrophobic mussel adhesive protein, and not the most enriched with 3,4-dihydroxyphenylalanine, effectively dries the surface and overcomes repulsive hydration forces to adsorb spontaneously to surfaces in preparation for adhesion.