Biyoinformatik ve Genetik Bölümü Koleksiyonu

Permanent URI for this collectionhttps://gcris.khas.edu.tr/handle/20.500.12469/46

Browse

Now showing 1 - 20 of 142

Citation Count: 0
"2-pirazolin yapısındaki yeni bir bileşiğin sentezi, moleküler modellemesi ve monoaminoksidaz inhibitörü etkisinin araştırılması"
(Türkiye Halk Sağlığı Kurumu, 2018) Yelekçi, Kemal; Uçar, Gülberk; Yelekçi, Kemal
Amaç: Nöromediatörlerin yıkımından sorumlu olan monoamin oksidaz (MAO) enziminin izoformlarının (MAO-A ve -B) birçok hastalık ile yakından ilişkili olduğu; MAO inhibitörlerinin depresyon, Parkinson ve Alzheimer hastalığı gibi hastalıkların tedavisinde kullanıldığı bilinmektedir. Grubumuzca daha etkin, tersinir ve az yan etkili yeni bir MAO inhibitörü (SH2U bileşiği) sentezlenmiş ve bu bileşiğin insan MAO enzimini (hMAO) inhibe etme yeteneği incelenmiştir. Ayrıca bu yeni bileşiğin hMAO ile etkileşimi, moleküler modelleme çalışmaları ile detaylı bir şekilde araştırılmıştır. Sentezlenen yeni bileşiğin hMAO’yu kuvvetli bir şekilde yarışmalı ve tersinir olarak inhibe ettiği bulunmuştur. Söz konusu bileşiğin Parkinson ve Alzheimer hastalıklarının tedavisinde ümit verici bir ilaç etken maddesi olabileceği düşünülmektedir. Yöntem: 3’,5’-Dikloro-2’-hidroksi asetofenon ile p-tolualdehit’in metanol içinde KOH varlığında reaksiyona girmesiyle 1-(3,5-dikloro-2-hidroksifenil)- 3-p-tolil prop-2-en-1-on (3’,5’-Dikloro-2’-hidroksi-4- metil şalkon) bileşiği sentez edilmiştir. Daha sonra elde edilen bu bileşiğin etanol içerisinde geri çeviren soğutucu altında izonikotinik asit hidrazit ile muamele edilmesiyle [3-(3,5-dikloro-2-hidroksifenil)-5-p-tolil-4,5- dihidropirazol-1-il] (piridin-4-il) metanon bileşiği sentez edilmiştir. Yapısı doğrulanan bu bileşiğin hMAO enzimi ile etkileşimi, ticari tayin kiti kullanılarak fluorometrik bir yöntemle incelenmiştir. Ayrıca, söz konusu yeni bileşik ile hMAO arasındaki etkileşimler, moleküler modelleme çalışmaları ile aydınlatılmıştır. Bulgular: Sentezlenen bileşiğin yapısı, IR, Mass, 1H-NMR ve elemental analiz yöntemleri kullanılarak doğrulanmıştır. Yapısı doğrulanan bu bileşiğin etkin, seçici, tersinir, toksik olmayan bir hMAO-B inhibitörü olduğu ve inhibisyonun yarışmalı olduğu görülmüştür. Moleküler yerleştirme programı kullanılarak bileşiğin hMAO-B enziminin aktif bölgesinde hangi amino asit yan zincirleri ile ne tür girişimleri yaptığı belirlenmiştir. Sonuç: Yeni sentezlenen SH2U bileşiği, hMAO-B enzimini kuvvetle, seçici, yarışmalı ve tersinir olarak inhibe etmiştir. Sentezlediğimiz bileşik, bilinen seçici ama tersinmez MAO-B inhibitörü olan selejilin’den daha etkin ve seçici, tersinir olarak hMAO-B enzimini inhibe etmiştir ve Parkinson ile Alzheimer hastalığı tedavisinde kullanılabilecek bir ilaç etken maddesi olarak ümit vadetmektedir.
Citation Count: 18
Absolute configuration and biological profile of pyrazoline enantiomers as MAO inhibitory activity
(Wiley, 2019) Yelekçi, Kemal; Sarıgül, Sevgi; Bultinck, Patrick; Herrebout, Wouter; Doğan, İlknur; Yelekçi, Kemal; Uçar, Gülberk; Kelekçi, Nesrin Gökhan
A new racemic pyrazoline derivative was synthesized and resolved to its enantiomers using analytic and semipreparative high-pressure liquid chromatography. The absolute configuration of both fractions was established using vibrational circular dichroism. The in vitro monoamine oxidase (MAO) inhibitory profiles were evaluated for the racemate and both enantiomers separately for the two isoforms of the enzyme. The racemic compound and both enantiomers were found to inhibit hMAO-A selectively and competitively. In particular the R enantiomer was detected as an exceptionally potent and a selective MAO-A inhibitor (K-i = 0.85 x 10(-3) +/- 0.05 x 10(-3) mu M and SI: 2.35 x 10(-5)) whereas S was determined as poorer compound than R in terms of K-i and SI (0.184 +/- 0.007 and 0.001). The selectivity of the enantiomers was explained by molecular modeling docking studies based on the PDB enzymatic models of MAO isoforms.
Citation Count: 7
Antifungal screening and in silico mechanistic studies of an in-house azole library
(2019) Sarı, Suat; Kart, Didem; Sabuncuoğlu, Suna; Doğan, İnci Selin; Özdemir, Zeynep; Bozbey, İrem; Gencel, Melis; Eşsiz, Şebnem; Reynisson, Jóhannes; Karakurt, Arzu; Saraç, Selma; Dalkara, Sevim
Systemic Candida infections pose a serious public health problem with high morbidity and mortality. C. albicans is the major pathogen identified in candidiasis; however, non-albicans Candida spp. with antifungal resistance are now more prevalent. Azoles are first-choice antifungal drugs for candidiasis; however, they are ineffective for certain infections caused by the resistant strains. Azoles block ergosterol synthesis by inhibiting fungal CYP51, which leads to disruption of fungal membrane permeability. In this study, we screened for antifungal activity of an in-house azole library of 65 compounds to identify hit matter followed by a molecular modeling study for their CYP51 inhibition mechanism. Antifungal susceptibility tests against standard Candida spp. including C. albicans revealed derivatives 12 and 13 as highly active. Furthermore, they showed potent antibiofilm activity as well as neglectable cytotoxicity in a mouse fibroblast assay. According to molecular docking studies, 12 and 13 have the necessary binding characteristics for effective inhibition of CYP51. Finally, molecular dynamics simulations of the C. albicans CYP51 (CACYP51) homology model's catalytic site complexed with 13 were stable demonstrating excellent binding.
Citation Count: 0
Atomic collisions and free lepton pair production
(2005) Güçlü, Mehmet Cem; Yılmaz, Melek
In this work we have calculated the total cross sections of electron-positron pair production for the collisions of fully stripped gold ions for various energies. We have also compared our calculation with other methods.
Citation Count: 18
Carboxylic acid derivatives display potential selectivity for human histone deacetylase 6: Structure-based virtual screening molecular docking and dynamics simulation studies
(Elsevier Science, 2018) Yelekçi, Kemal; Yelekçi, Kemal
Human histone deacetylase 6 (HDAC6) has been shown to play a major role in oncogenic cell transformation via deacetylation of alpha-tubulin making it a viable target of anticancer drug design and development. The crystal structure of HDAC6 catalytic domain 2 has been recently made available providing avenues for structure-based drug design campaign. Here in our continuous effort to identify potentially selective HDAC6 inhibitors structure-based virtual screening of similar to 72 461 compounds was carried out using Autodock Vina. The top 100 compounds with calculated Delta G < -10 kcal/mol were manually inspected for binding mode orientation. Furthermore the top 20 compounds with reasonable binding modes were evaluated for selectivity by further docking against HDAC6 and HDAC7 using Autodock4. Four compounds with a carboxylic fragment displayed potential selectivity for HDAC6 over HDAC7 and were found to have good druglike and ADMET properties. Their docking complexes were then submitted to 10 ns-molecular dynamics (MD) simulation using nanoscale MD (NAMD) software to examine the stability of ligand binding modes. These predicted inhibitors remained bound to HDAC6 in the presence of water and ions and the root-mean-square deviation (RMSD) radius of gyration (Rg) and nonbond distance (protein-ligand) profiles suggested that they might be stable over time of the simulation. This study may provide scaffolds for further lead optimization towards the design of HDAC6 inhibitors with improved selectivity. (C) 2018 Elsevier Ltd. All rights reserved.
Citation Count: 16
Cation Effect on Slow Release from Alginate Beads: A Fluorescence Study
(Springer/Plenum Publishers, 2014) Kaygusuz, Hakan; Erim, F. Bedia; Pekcan, Önder; Evingür, Gülşen Akin
In this study spherical alginate beads containing pyranine (P-y) as a fluorescence probe were prepared by ionotropic gelation of a sodium alginate solution. The steady state fluorescence technique was used to study pyranine release from the alginate beads crosslinked with calcium barium and aluminum ions respectively. The slow release of P-y was observed with the time drive mode of the spectrophotometer at 512 nm. Fluorescence emission intensity (I-p) from P-y was monitored during the release process and the encapsulation efficiency (EE) of pyranine from the alginate beads was calculated. The Fickian Diffusion model was used to measure the release coefficients D-sl. It was seen that the slow release coefficients of pyranine from the alginate beads crosslinked with Ca2+ Ba2+ and Al3+ ions increased in the following order: D-sl (Al3+)> D-sl (Ca2+)> D-sl (Ba2+). In contrast the initial amount of pyranine and EE into the beads showed the reverse behavior.
Citation Count: 2
Characterization of MWCNT-TiO2 Qps and TiO2 QDs in self-assembled films
(Elsevier, 2017) Akkaya Arier, Ümit Özlem; Uysal, Bengü Özuğur
In this study the solution which includes TiO2 quantum dots (QDs) was mixed with the multi-wall carbon nanotubes (MWCNTs) to prepare MWCNT-TiO2 QDs composite films. The effect of microstructures on the structural and optical properties of MWCNT-TiO2 QDs composite films was evaluated. The activation energy for crystallite growth of TiO2 QDs which are produced in brookite phases was calculated as 20.3 kJ/mol. The properties of MWCNT-TiO2 QDs composite films were characterized by X-ray diffraction (XRD) scanning electron microscopy (SEM) atomic force microscopy (AFM) and ultraviolet-visible absorption spectroscopy (UV-vis). (C) 2017 Elsevier GmbH. All rights reserved.
Citation Count: 0
Classification Of Distinct Conformers Of Beta < 2-Adrenergic Receptor (Beta 2-AR) Based On Binding Affinity Of Ligands Through Docking Studies
(Amer Chemical Soc, 2016) Akten, Ebru Demet; Dilcan, Gonca
B2AR reseptörü, akciğerlerin rahatlamasında ve kardiyovasküler fizyolojide rol oynamasıyla önemli bir ilaç hedefidir. Bu çalışmada, çeşitli B2AR konformasyonlarını aktif veya inaktif olarak sınıflandırmak amacıyla, aktivitesi bilinen ligantlar seçilerek onların bağlanma şekillerine göre bir sınıflandırma stratejisi oluşturulmuştur. Önceki bir çalışmada gerçekleştirilen, reseptörün inaktif halinin 2.8 μs'lik MD simülasyonunda, ligandın bağlanma bölgesinin farklı konformasyonları elde edilmiştir. Snapshotlar derlenerek bağlanma bölgesindeki beş anahtar rezidünün RMSD değerlerine göre gruplandırılmıştır. Toplamda 13 farklı konformasyon elde edilmiş ve 5 agonist, 4 ters agonist ve 4 antagonist molekülü her bir konformasyona ayrı ayrı ve 7 farklı skor fonksiyonu kullanılarak dock edilmiştir. En iyi yerleşen konformasyonlar bağlanma bölgesindeki anahtar rezidülerle olan yakınlığına göre seçilmiş ve hesaplanmıştır. Anahtar bölgeye yaklaşamayanlar elenmiş, kalanlar ise skor değerlerine göre sıralanmıştır. Bu sınıflandırma, kritik değerlendirme yapabilmek için MD konformasyonlarından önce aktivitesi bilinen aktif/inaktif kristal yapılara uygulanmıştır. Her skor fonksiyonu tarafından seçilen ve ilk 5'te bulunan MD konformasyonları aktif ve inaktif olarak sınıflandırılmıştır. Son olarak, MD konformasyonlarının ayırt ediciliğini analiz edebilmek için, seçilen bu konformasyonlar ile küçük bir dataset kullanılarak sanal tarama yapılmıştır. MD konformasyonlarının inaktif kristal yapıya göre antagonist/ters agonistler için daha seçici olduğu gözlemlenmiştir. Reseptörün alternatif konformasyonlarını üretmek ve onları sınıflandırmak, genellikle tek bir snaphot X-ray örneği ile sınırlandırılmış ilaç tasarımı çalışmalarında önemli rol oynamaktadır.
Citation Count: 0
Collective enhancement of nuclear state densities by the shell model Monte Carlo approach
(IOP Publishing Ltd, 2015) Özen, Cem; Alhassid, Yoram; Nakada, Hitoshi
The shell model Monte Carlo (SMMC) approach allows for the microscopic calculation of statistical and collective properties of heavy nuclei using the framework of the configuration-interaction shell model in very large model spaces. We present recent applications of the SMMC method to the calculation of state densities and their collective enhancement factors in rare-earth nuclei.
Citation Count: 1
Collectivity in Heavy Nuclei in the Shell Model Monte Carlo Approach
(EDP Sciences, 2014) Özen, Cem; Alhassid, Yoram; Nakada, Hitoshi
The microscopic description of collectivity in heavy nuclei in the framework of the configuration-interaction shell model has been a major challenge. The size of the model space required for the description of heavy nuclei prohibits the use of conventional diagonalization methods. We have overcome this difficulty by using the shell model Monte Carlo (SMMC) method which can treat model spaces that are many orders of magnitude larger than those that can be treated by conventional methods. We identify a thermal observable that can distinguish between vibrational and rotational collectivity and use it to describe the crossover from vibrational to rotational collectivity in families of even-even rare-earth isotopes. We calculate the state densities in these nuclei and find them to be in close agreement with experimental data. We also calculate the collective enhancement factors of the corresponding level densities and find that their decay with excitation energy is correlated with the pairing and shape phase transitions.
Citation Count: 0
COMP 297-Experimental and molecular docking simulation studies of Histone deacetylases (HDACs) enzyme inhibitors
(Amer Chemical Soc, 2007) Yelekçi, Kemal; Bora, Gamze; Dayangaç-Erden, Didem; Ayhan, Peruze; Dalkara, Sevim; Demir, Ayhan S.; Erdem-Yurter, Hayat
[Abstract Not Available]
Citation Count: 0
Comparison of cation effects on phase transitions of kappa and iota carrageenan
(European Polymer Federation, 2010) Tari, Özlem; Pekcan, Önder
Phase transitions of kappa and iota carrageenan in KCl NaCl and CaCl2 solutions were separately studied during heating and cooling processes by using fluorescence technique. Scattered light I-SC and fluorescence intensity I was monitored against temperature to determine the critical transition temperatures and exponents. Kappa and iota carrageenans with monovalent (KCl NaCl) salt system presented only coil to double helix (c-h) and double helix to coil (h-c) transitions upon cooling and heating processes respectively. Two transition regions were observed in both heating and cooling of the iota carrageenan in CaCl2 solution while in kappa carrageenan only (c-h) and (h-c) transitions was detected. During heating dimers decompose into double helices by making (d-h) transition. At the high temperature region (h-c) transition takes place. During cooling back transitions repeat themselves. A hysteresis was observed between (h-c) and (c-h) for the kappa and iota carrageenan salt system (except CaCl2) respectively. Dimer to double helix (d-h) and double helix to dimer (h-d) transitions were observed for iota carrageenan in CaCl2 salt. The gel fraction exponent beta was measured and found to be in accord with the classical Flory-Stockmayer Model for both kappa and iota carrageenan salt systems.
Citation Count: 6
A comparison of fluorescence and UV-visible spectrometry techniques for thermal phase transitions of agarose gels
(Springer, 2015) Arda, Ertan; Kara, Selim; Mergen, Ömer Bahadır; Pekcan, Önder
In this study thermoreversible phase transitions of high (HMP) and low (LMP) melting point agarose gels were investigated by using the UV-vis and fluorescence spectroscopy techniques. Pyranine was added to the aqueous solution of agarose as a fluorescence-probe. Transmitted light (I (tr)) and fluorescence emission (I (fl)) intensities from the gel samples with different agarose concentrations were monitored during the heating (gel-sol) and cooling (sol-gel) processes. For the both techniques gel-sol (T (gs)) and sol-gel (T (sg)) transition temperatures were determined from the first derivatives of the sigmoidal transition paths. It was observed that the critical transition temperatures obtained from UV-vis and fluorescence data slightly increased depending on the agarose type and concentration and those values were found to be in accord with each other. Transition activation energies were determined using the Arrhenius type equation and were found to be strongly correlated with the agarose content in the gel system. The produced gel-sol (Delta E (gs)) and sol-gel (Delta E (sg)) transition energies from the fluorescence data were found to be lower than that of the UV-vis data which was attributed to the temperature-dependent fluorescence quenching effect.
Citation Count: 21
Conductivity percolation of carbon nanotubes (CNT) in polystyrene (PS) latex film
(Canadian Science Publishing Nrc Research Press, 2010) Uğur, Şaziye; Yargı, Önder; Pekcan, Önder
In this study the effect of multiwalled carbon nanotubes (MWNT) on film formation behaviour and electrical conductivity properties of polystrene (PS) latex film was investigated by using the photon transmission technique and electrical conductivity measurements. Films were prepared by mixing PS latex with different amounts of MWNTs varying in the range between 0 and 20 wt%. After drying MWNT content films were separately annealed above the glass transition temperature (T-g) of PS ranging from 100 to 270 degrees C for 10 min. To monitor film formation behavior of PS-MWNT composites transmitted light intensity I-tr was measured after each annealing step. The surface conductivity of annealed films at 170 degrees C was measured and found to increase dramatically above a certain fraction of MWNT (4 wt%) following the percolation theory. This fraction was defined as the percolation threshold of conductivity R-c. The conductivity scales with the mass fraction of MWNT as a power law with exponent 2.27 which is extremely close to the value of 2.0 predicted by percolation theory. In addition the increase in I-tr during annealing was explained by void closure and interdiffusion processes. Film formation stages were modeled and the corresponding activation energies were measured.
Citation Count: 2
Conductivity Percolation of Carbon Nanotubes in Polyacrylamide Gels
(Intech Europe, 2011) Pekcan, Önder; Evingür, Gülşen Akın
[Abstract Not Available]
Citation Count: 7
Controlling the growth of particle size and size distribution of silica nanoparticles by the thin film structure
(Springer, 2012) Uysal, Bengü Özuğur; Tepehan, Fatma Zehra
Nanostructured silicondioxide thin films were prepared by sol-gel spin coating technique. The SiO2 films were made using a conventional mixture of tetraethoxysilane (TEOS) deionized water and ethanol with various NH3/TEOS ratios. The nanostructured silica films were made using a mixture of the SiO2 sol and regular SiO2 sol to control the enlargement of the particles inside the films. The structural morphological and optical characterizations of the as-deposited and annealed films were carried out using X-ray diffraction (XRD) atomic force microscopy scanning electron microscopy NKD spectrophotometer and ultraviolet-visible (UV-vis) spectroscopy. The transmittance data of the infrared spectra of the films were recorded using an FT-IR Spectrometer. The XRD studies showed that as-deposited films were amorphous and the formation of the alfa-cristobalite phase of the silica film was investigated at annealing temperature close to 1100 A degrees C. Optical properties of the transmittance spectra in the s and p-polarization modes were collected. Refractive indices and extinction coefficients were determined with respect to the NH3/TEOS ratios in the compositions of the films. Optical cut-off wavelength values were investigated from the extrapolation of the absorbance spectra which was estimated from the UV-vis spectroscopy measurements. A red shift in the absorption threshold indicated that the size of silica nanoparticles was increased by an increase in the NH3/TEOS volume ratio from 1:64 to 1:8.
Citation Count: 2
Corrected Panel-Reactive Antibody Positivity Rates for Hypersensitized Patients in Turkish Population With Calculated Panel-Reactive Antibody Software
(Elsevier Science Inc, 2017) Yelekçi, Kemal; Akgül, Sebahat Usta; Öğret, Yeliz; Çiftçi, Hayriye Şentürk; Bayraktar, Adem; Bakkaloğlu, Hüseyin; Çalışkan, Yaşar Kerem; Yelekçi, Kemal; Türkmen, Aydin; Aydın, Ali Emin; Oğuz, Fatma Savran; Çarin, Mahmut Nezih; Aydın, Filiz
however the rate was 86.2% using the cPRA. Discussion. cPRA shows the rate of the rejected donors according to all unacceptable antigens. The need for a list of unacceptable antigens in place of the PRA positivity rate is a real change in the sensitization-dependent calculation as cPRA positivity rate. Conclusion. In principal implementation of cPRA will encourage many centers and laboratories to adopt a standard measurement of sensitization in Turkey. It will increase the chances of better donor match particularly for hypersensitized patients by the creation of an unacceptable mismatch program using cPRA software.
Citation Count: 22
Critical Exponents of Gelation and Conductivity in Polyacrylamide Gels Doped by Multiwalled Carbon Nanotubes
(Taylor & Francis Ltd, 2010) Aktas, Demet Kaya; Evingür, Gülşen Akin; Pekcan, Önder
Polyacrylamide (PAM) doped by multiwalled carbon nanotube (MWNT) gels were prepared with different amounts of MWNTs varying in the range between 0.1 and 15 wt%. The PAM-MWNT composite gels were characterized by the steady state fluorescence technique (SSF). The alternative electrical conductivity (AC) of PAM-MWNT composite gels was measured by the dielectric spectroscopy technique. Observations around the gel point t(gel) for PAM-MWNTs composite gels showed that the gel fraction exponent beta obeyed the percolation result. The critical exponent r of AC electrical conductivity for the composite PAM-MWNT gel was also measured and found to be about 2.0 which agrees with a random resistor network. (C) Koninklijke Brill NV Leiden 2010
Citation Count: 19
Critical Exponents of Kappa Carrageenan in the Coil-Helix and Helix-Coil Hysteresis Loops
(Taylor & Francis Inc, 2009) Tarı, Özlem; Kara, Selim; Pekcan, Önder
The steady-state fluorescence technique was used to study coil-helix (sol-gel) and helix-coil (gel-sol) transitions of the kappa carrageenan-water system with various carrageenan contents. Fluorescence (I) and scattered light (I-sc) intensities were measured against temperature to determine critical phase transition temperatures and exponents. It was observed that the coil-helix transition temperatures T-ch were much lower than the helix-coil (T-hc) transition temperatures due to the hysteresis of the phase transition loops. The gel fraction exponent (beta) was measured and found to be in accord with the classical Flory-Stockmayer model.
Citation Count: 15
Critical Exponents of Photoinitiated Gelation at Different Light Intensities
(Taylor & Francis Inc, 2009) Doğruyol, Zekeriya; Arsu, Nergis; Pekcan, Önder
A photo-differential scanning calorimetric (Photo-DSC) technique was used to study the photoinitiated radical polymerization of a 75% epoxy diacrylate (EA) and 25% tripropyleneglycoldiacrylate (TPGDA) mixture with 2-mercaptothioxanthone (TX-SH) as photoinitiator by using different light intensities. Photopolymerization reactions were carried out under identical conditions of temperature and initiator concentration. It was observed that all conversion curves during gelation at various Might intensities present good sigmoidal behavior as predicted by the percolation model. Observations around the critical time called the glass transition point (t(g)) taken for polymerization to reach the maximum rate (R-pmax) show that the gel fraction exponents beta obeyed the universal percolation picture. On the other hand R-pmax t(g) and final conversion values were found to be dependent on the UV light intensity.

Browse

Browsing Biyoinformatik ve Genetik Bölümü Koleksiyonu by WoS Q "N/A"