Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Article Citation - WoS: 5Citation - Scopus: 5The Designing of a Gel Formulation With Chitosan Polymer Using Liposomes as Nanocarriers of Amphotericin B for a Non-Invasive Treatment Model of Cutaneous Leishmaniasis(Springer, 2022) Gürbüz, Nergiz; Çetin Uyanıkgil, Emel Öykü; Özbel, Yusuf; Töz, SerayPurpose Leishmaniasis is a disease caused by different Leishmania spp., which are transmitted to humans by a bite of infected female sand flies. Cutaneous leishmaniasis (CL, oriental sore), visceral leishmaniasis (VL), and mucocutaneous leishmaniasis (MCL) are three main clinical forms, however, only CL and VL are seen in Turkey. Cutaneous leishmaniasis is characterized by skin lesion(s) and is one of the most important vector-borne diseases in Turkey with over 2000 cases reported annually in 40 out of 81 provinces. The treatment is usually made invasively and painfully by intralesional injection of pentavalent antimony compounds. Non-invasive and innovative treatment methods are needed as aimed in this study. Methods In the present study, one of the classical antileishmanial drugs, amphotericin B (AmB), encapsulated in liposomes was evaluated using non-invasive design based on chitosan, which is a nontoxic, biocompatible and biodegradable polymer. To avoid the invasive effect of conventional intralesional needle application, the drug was encapsulated in liposomes and incorporated into a chitosan gel for applying topically on the skin lesion. The efficacy of encapsulation of amphotericin B into liposomes and the drug release from liposomes were studied. The chitosan gel was evaluated for viscosity, flowability, appearance and pH. The efficacy of the drug embedded into chitosan gel, liposomal AmB alone and chitosan gel alone in four different concentrations was also tested using Leishmania spp. promastigotes in vitro. Results The findings have shown that AmB was encapsulated into the liposomes with high efficiency (86.6%) and long-term physical and chemical stability. Therefore, designed liposomal formulation was suitable for sustained release. The appearance of the drug-embedded chitosan gel was transparent and appropriate. Chitosan gels showed non- Newtonian behavior and plastic flow. The liposomal AmB also showed higher efficacy with no parasites in all concentrations while drug embedded into chitosan gel and chitosan gel alone were effective in two higher concentrations. The lower efficacy of the drug-embedded chitosan gel in 24 h in in-vitro study was probably due to slow release of the drug. Conclusion The gel design created in this study will provide ease of use for the lesions of CL patients that do not have a specific number, size, and shape. Follow-up studies by the ex-vivo macrophage infection model with Leishmania intracellular amastigote forms and Leishmania-infected animal models are needed to understand the present design's efficacy better.Article Citation - WoS: 6Citation - Scopus: 6Investigation of Interactions of Doxorubicin With Purine Nucleobases by Molecular Modeling(Springer, 2022) Akdeniz, Esra Şahin; Selçuki, CenkDoxorubicin, an anthracycline antibiotic with anti-tumor activity, is produced by the bacterium Streptomyces peucetius. The interactions between doxorubicin and genetic material and the details of the intercalation with DNA have been controversial issues. Thus, the interactions of doxorubicin with purine nucleobases were studied by quantum mechanical methods. Initially, conformer analyses of doxorubicin were performed with Spartan 08 software and 319 different conformers from 422 initial structures for doxorubicin were obtained. Geometry optimizations and frequency analyses were performed for each structure using density functional theory (DFT) at B3LYP/6-31G** level using Gaussian 09 software. The most stable 20 conformers of doxorubicin and tautomers of purine nucleobases were optimized again with ɷB97XD/6-31G** level and their interactions were also analyzed at the same level. The Discovery Studio 3.5 Visualizer was used to draw the initial and optimized structures of investigated geometries. The noncovalent interactions (NCIs) were visualized by calculating reduced density gradient (RDG) with Multiwfn program. The color-filled isosurfaces and RDG scatter maps of most stable interaction geometries were plotted by Visual Molecular Dynamics (VMD) software and Gnuplot 5.3 software, respectively. This study showed that adenine, guanine, and hypoxanthine nucleobases interact with doxorubicin by forming strong hydrogen bonds and π-π interactions. Considering the normal cellular conditions, the effect of solvent (water) on the interaction geometries were also analyzed and when compared to gas phase it was determined that the movements of the molecules were restricted and there was a minimal change between initial and optimized structures in the aqueous phase.Article Gas-Phase Fragmentation Reactions of A7 Ions Containing a Glutamine Residue(Wiley-Blackwell, 2021) Atik, Ahmet; Arslanoğlu, Alper; Yalçın, Talat; Atik, Ahmet; Arslanoğlu, Alper; Yalçın, TalatThe gas-phase fragmentation reactions of the a7 ions derived from glutamine (Q) containing model heptapeptides have been studied in detail with low-energy collision-induced dissociation (CID) tandem mass spectrometry (MS/MS). Specifically, the positional effect of the Q residue has been investigated on the fragmentation reactions of a7 ions. The study involves two sets of permuted isomers of the Q containing model heptapeptides. The first set contains the QAAAAAA sequence, and the second set involves of QYAGFLV sequence, where the position of the Q residue is changed from N- to C-terminal gradually for both peptide series. An intense loss of ammonia from the a7 ions followed by internal amino acid eliminations strongly supports forming the imine-amides structure via cyclization/rearrangement reaction for all studied a7 ions. This is in agreement with the pioneering study reported by Bythell et al. (2010, 10.1021/ja101556g). A novel rearrangement reaction is detected upon fragmentation of imine-amide structure, which yields a protonated C-terminal amidated hexapeptide excluding the Q residue. A possible fragmentation mechanism was proposed to form the protonated C-terminal amidated hexapeptide, assisted via nucleophilic attack of the side chain amide nitrogen of the Q residue on its N-protonated imine carbon atom of the rearranged imine-amide structure. Highlights: The gas-phase fragmentation reactions of a7 ions obtained from protonated model peptides containing glutamine residue were studied by ESI-MS/MS. A rearranged imine-amide structure is the predominant even for a7 ions. Novel rearrangement reaction is observed which forms a protonated C-terminal amidated hexapeptide excluding Q residue upon fragmentation of the imine-amide structure.