Araştırma Çıktıları | WoS | Scopus | TR-Dizin | PubMed
Permanent URI for this communityhttps://hdl.handle.net/20.500.14719/1741
Browse
5 results
Search Results
Publication Metadata only AT1 antagonists: A patent review (2008 - 2012)(2013) Mavromoustakos, Thomas M.; Agelis, George; Durdagi, Serdar; Mavromoustakos, Thomas M., Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece; Agelis, George, Department of Chemistry, University of Patras, Rio, Greece, Eldrug S.A., Patra, Greece; Durdagi, Serdar, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, TurkeyIntroduction: For two decades a class of pharmaceutical molecules with proved beneficial therapeutic properties, especially in hypertension, has been introduced in the market aiming to specifically prevent the detrimental effects of the peptide hormone Angiotensin II at the AT1 receptor. The prototype of this class was losartan and based on its structure, several drugs were launched and also called 'Sartans'. New structural features on these molecules can provide multi-target properties in the RAS or other systems. New methodologies were developed for the treatment of hypertension utilizing either AT1 antagonists alone or as cocktails. Areas covered: In this review article, authors aim to cover information provided by patents of the years 2008-2012. The rationale of writing this review article is to cover the most important patents which can forward the field with new important discoveries. Expert opinion: From the patent investigation it is clear that new areas on the subject are still offered for new discoveries. New structural features can be still considered in the synthetic compounds that can advance the knowledge and beneficial effects on diseases related to Angiotensin II and AT1 receptor. There is era also for new formulations (i.e., cyclodextrins, polymers and liposomes). The multitarget approach can be further strengthened and more combinations can be sought in the rational drug design for seeking cocktails. Furthermore, the revealing of the complexity of the RAS offers new avenues for novel targets and this must not be overlooked. © 2013 Informa UK, Ltd. © 2013 Elsevier B.V., All rights reserved.Publication Metadata only Current status of multiscale simulations on GPCRs(Elsevier Ltd, 2019) Durdagi, Serdar; Doğan, Berna; Erol, Ismail; Kayık, Gülru; Aksoydan, Busecan; Durdagi, Serdar, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, Turkey, Neuroscience Program, Bahçeşehir Üniversitesi, Istanbul, Turkey; Doğan, Berna, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, Turkey; Erol, Ismail, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, Turkey, Department of Chemistry, Gebze Teknik Üniversitesi, Gebze, Turkey; Kayık, Gülru, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, Turkey; Aksoydan, Busecan, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, Turkey, Neuroscience Program, Bahçeşehir Üniversitesi, Istanbul, TurkeyMembrane receptors couple signaling pathways using various mechanisms. G Protein-Coupled Receptors (GPCRs) represent the largest class of membrane proteins involved in signal transduction across the biological membranes. They are essential targets for cell signaling and are of great commercial interest to the pharmaceutical industry. Recent advances made in molecular biology and computational chemistry offer a range of simulation and multiscale modeling tools for the definition and analysis of protein–ligand, protein–protein, and protein–membrane interactions. The development of new techniques on statistical methods and free energy simulations help to predict novel optimal ligands, G protein specificity and oligomerization. The identification of the ligand-binding activation mechanisms and atomistic determinants as well as the interactions of intracellular binding partners that bind to GPCR targets in different coupling states will provide greater safety in human life. In this review, recent approaches and applications of multiscale simulations on GPCRs were highlighted. © 2019 Elsevier B.V., All rights reserved.Publication Metadata only Oligomerization and cooperativity in GPCRs from the perspective of the angiotensin AT1 and dopamine D2 receptors(Elsevier Ireland Ltd, 2019) Durdagi, Serdar; Erol, Ismail; Salmas, Ramin Ekhteiari; Aksoydan, Busecan; Kantarcioglu, Isik; Durdagi, Serdar, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, Turkey, Neuroscience Program, Bahçeşehir Üniversitesi, Istanbul, Turkey; Erol, Ismail, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, Turkey, Department of Chemistry, Gebze Teknik Üniversitesi, Gebze, Turkey; Salmas, Ramin Ekhteiari, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, Turkey; Aksoydan, Busecan, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, Turkey, Neuroscience Program, Bahçeşehir Üniversitesi, Istanbul, Turkey; Kantarcioglu, Isik, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, Turkey, Bioengineering Program, Bahçeşehir Üniversitesi, Istanbul, TurkeyG Protein-Coupled Receptors (GPCRs) can form homo- and heterodimers or constitute higher oligomeric clusters with other heptahelical GPCRs. In this article, multiscale molecular modeling approaches as well as experimental techniques which are used to study oligomerization of GPCRs are reviewed. In particular, the effect of dimerization/oligomerization to the ligand binding affinity of individual protomers and also on the efficacy of the oligomer are discussed by including diverse examples from the literature. In addition, possible allosteric effects that may emerge upon interaction of GPCRs with membrane components, like cholesterol, is also discussed. Investigation of these above-mentioned interactions may greatly contribute to the candidate molecule screening studies and development of novel therapeutics with fewer adverse effects. © 2021 Elsevier B.V., All rights reserved.Publication Metadata only Challenges and limitations in the studies of glycoproteins: A computational chemist's perspective(John Wiley and Sons Inc, 2022) Balli, Oyku Irem; Uversky, Vladimir N.; Durdagi, Serdar; Coskuner-Weber, Orkid; Balli, Oyku Irem, Molecular Biotechnology, Turkish-German University, Istanbul, Turkey; Uversky, Vladimir N., Byrd Alzheimer’s Center and Research Institute, Tampa, United States; Durdagi, Serdar, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, Turkey; Coskuner-Weber, Orkid, Molecular Biotechnology, Turkish-German University, Istanbul, TurkeyExperimenters face challenges and limitations while analyzing glycoproteins due to their high flexibility, stereochemistry, anisotropic effects, and hydration phenomena. Computational studies complement experiments and have been used in characterization of the structural properties of glycoproteins. However, recent investigations revealed that computational studies face significant challenges as well. Here, we introduce and discuss some of these challenges and weaknesses in the investigations of glycoproteins. We also present requirements of future developments in computational biochemistry and computational biology areas that could be necessary for providing more accurate structural property analyses of glycoproteins using computational tools. Further theoretical strategies that need to be and can be developed are discussed herein. © 2022 Elsevier B.V., All rights reserved.Publication Metadata only Review on In Silico Methods, High-throughput Screening Techniques, and Cell Culture Based In Vitro Assays for SARS-CoV-2(Bentham Science Publishers, 2022) Çetin, Yuksel; Aydinlik, Seyma; Gungor, Aysen; Kan, Tugce; Avşar, Timuçin; Durdagi, Serdar; Çetin, Yuksel, Genetic Engineering and Biotechnology Institute, TUBITAK Marmara Research Center, Gebze, Turkey; Aydinlik, Seyma, Genetic Engineering and Biotechnology Institute, TUBITAK Marmara Research Center, Gebze, Turkey; Gungor, Aysen, Genetic Engineering and Biotechnology Institute, TUBITAK Marmara Research Center, Gebze, Turkey; Kan, Tugce, Genetic Engineering and Biotechnology Institute, TUBITAK Marmara Research Center, Gebze, Turkey; Avşar, Timuçin, Department of Biology, Bahçeşehir Üniversitesi, Istanbul, Turkey; Durdagi, Serdar, Department of Biophysics, Bahçeşehir Üniversitesi, Istanbul, TurkeyThe COVID-19 outbreak caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to have high incidence and mortality rate global-ly. To meet the increasingly growing demand for new therapeutic drugs and vaccines, researchers are developing different diagnostic techniques focused on screening new drugs in clinical use, developing an antibody targeting a SARS-CoV-2 receptor, or interrupting infection/replication mechanisms of SARS-CoV-2. Although many prestigious research publications are addressing this subject, there is no open access platform where all experimental techniques for COVID-19 research can be seen as a whole. Many researchers have accelerated the development of in silico methods, high-throughput screening tech-niques, and in vitro assays. This development has played an important role in the emergence of improved, innovative strategies, including different antiviral drug development, new drug discovery protocols, combinations of approved drugs, and setting up new drug classes during the COVID-19 outbreak. Hence, the present review discusses the current literature on these modalities, including virtual in silico methods for instant ligand-and target-driven based techniques, nucleic acid amplification tests, and in vitro models based on sensitive cell cultures, tissue equivalents, organoids, and SARS-CoV-2 neutralization systems (lentiviral pseudotype, viral isolates, etc.). This pack of complementary tests informs researchers about the accurate, most relevant emerging techniques available and in vitro assays allow them to understand their strengths and limitations. This review could be a pioneer reference guide for the development of logical algorithmic approaches for new drugs and vaccine strategies against COVID-19. © 2023 Elsevier B.V., All rights reserved.