Dejana Popović, Bojana Popović, Bosiljka Plećaš‐Solarović, Vesna Pešić, Vidan Marković, Stanimir Stojiljković, Vladan Vukčević, Ivana Petrović, Marko Banović, Milan Petrović, Bosiljka Vujisić-Tešić, Miodrag Ostojić, Arsen Ristić, Svetozar Damjanović,
Brain natriuretic peptide (NT-pro-BNP) was implicated in the regulation of hypothalamic–pituitary–adrenocortical (HPA) responses to psychological stressors. However, HPA axis activation in different physical stress models and its interface with NT-pro-BNP in the prediction of cardiopulmonary performance is unclear. Cardiopulmonary test on a treadmill was used to assess cardiopulmonary parameters in 16 elite male wrestlers (W), 21 water polo player (WP) and 20 sedentary age-matched subjects (C). Plasma ...
Tópico(s): Cardiovascular and exercise physiology
2013 - Elsevier BV | Peptides
Claire Dobson, Paul W. A. Devine, Jonathan J. Phillips, Daniel R. Higazi, Christopher Lloyd, Bojana Popovic, Joanne Arnold, Andrew Buchanan, Arthur Lewis, Joanne Goodman, Christopher F. van der Walle, Peter Thornton, Lisa Vinall, David Lowne, Anna Aagaard, Lise‐Lotte Olsson, Anna Ridderstad Wollberg, Fraser Welsh, Theodoros K. Karamanos, Clare L. Pashley, M.G. Iadanza, Neil A. Ranson, Alison E. Ashcroft, Alistair D. Kippen, Tristan J. Vaughan, Sheena E. Radford, David C. Lowe,
Abstract Uncontrolled self-association is a major challenge in the exploitation of proteins as therapeutics. Here we describe the development of a structural proteomics approach to identify the amino acids responsible for aberrant self-association of monoclonal antibodies and the design of a variant with reduced aggregation and increased serum persistence in vivo. We show that the human monoclonal antibody, MEDI1912, selected against nerve growth factor binds with picomolar affinity, but undergoes ...
Tópico(s): Viral Infectious Diseases and Gene Expression in Insects
2016 - Nature Portfolio | Scientific Reports
Bojana Popovic, J. Breed, D. Gareth Rees, Matthew Gardener, Lisa Vinall, Benjamin Kemp, Jennifer Spooner, Jennifer Keen, Ralph Minter, Ferzan Uddin, Gene Colice, T. Wilkinson, Tristan J. Vaughan, Richard May,
Interleukin (IL)-13 is a pleiotropic T helper type 2 cytokine frequently associated with asthma and atopic dermatitis. IL-13-mediated signalling is initiated by binding to IL-13Rα1, which then recruits IL-4Rα to form a heterodimeric receptor complex. IL-13 also binds to IL-13Rα2, considered as either a decoy or a key mediator of fibrosis. IL-13-neutralising antibodies act by preventing IL-13 binding to IL-13Rα1, IL-4Rα and/or IL-13Rα2. Tralokinumab (CAT-354) is an IL-13-neutralising human IgG4 monoclonal ...
Tópico(s): Immune Cell Function and Interaction
2016 - Elsevier BV | Journal of Molecular Biology
James B. Dunbar, Konrad Krawczyk, Jinwoo Leem, Claire Marks, Jarosław Nowak, Cristian Regep, Guy Georges, Sebastian Kelm, Bojana Popovic, Charlotte M. Deane,
SAbPred is a server that makes predictions of the properties of antibodies focusing on their structures. Antibody informatics tools can help improve our understanding of immune responses to disease and aid in the design and engineering of therapeutic molecules. SAbPred is a single platform containing multiple applications which can: number and align sequences; automatically generate antibody variable fragment homology models; annotate such models with estimated accuracy alongside sequence and structural ...
Tópico(s): vaccines and immunoinformatics approaches
2016 - Oxford University Press | Nucleic Acids Research
E. Suzanne Cohen, Ian C. Scott, Jayesh B. Majithiya, Laura Rapley, Benjamin Kemp, Elizabeth England, D. Gareth Rees, Catherine L. Overed‐Sayer, Joanne Woods, Nicholas J. Bond, Christel Séguy Veyssier, Kevin J. Embrey, Dorothy A. Sims, Michael Snaith, Katherine A. Vousden, Martin Strain, Denice T. Y. Chan, Sara Carmen, Catherine E. Chaillan Huntington, Liz Flavell, Jianqing Xu, Bojana Popovic, Christopher E. Brightling, Tristan J. Vaughan, Robin Butler, David C. Lowe, Daniel R. Higazi, Dominic J. Corkill, Richard May, Matthew A. Sleeman, Tomas Mustelin,
Abstract In response to infections and irritants, the respiratory epithelium releases the alarmin interleukin (IL)-33 to elicit a rapid immune response. However, little is known about the regulation of IL-33 following its release. Here we report that the biological activity of IL-33 at its receptor ST2 is rapidly terminated in the extracellular environment by the formation of two disulphide bridges, resulting in an extensive conformational change that disrupts the ST2 binding site. Both reduced (active) ...
Tópico(s): Eosinophilic Esophagitis
2015 - Nature Portfolio | Nature Communications
Amy E. Joubert, Michelle L. Moulds, Aliza Werner‐Seidler, Maria J. Sharrock, Bojana Popović, Jill M. Newby,
Abstract Objectives Rumination and worry have been implicated in the onset, severity, maintenance and relapse risk of depression and anxiety disorders. Despite this, little research has examined individuals' personal experiences of these processes. This study investigates how individuals experience these processes, which will provide insight into these common features of mental disorders and inform the development of an online intervention specifically targeting rumination and worry. Design An online ...
Tópico(s): Child and Adolescent Psychosocial and Emotional Development
2022 - Wiley | British Journal of Clinical Psychology
Kalliopi Skamaki, Stéphane Emond, Matthieu Chodorge, John L. Andrews, D. Gareth Rees, Daniel A. Cannon, Bojana Popovic, Andrew Buchanan, Ralph Minter, Florian Hollfelder,
Significance Insertion/deletion (InDel) mutations play key roles in genome and protein evolution. Despite their prominence in evolutionary history, the potential of InDels for changing function in protein engineering by directed evolution remains unexplored. Instead point mutagenesis is widely used. Here we create antibody libraries containing InDels and demonstrate that affinity maturation can be achieved in this way, establishing an alternative to the point mutation strategies employed in all previous ...
Tópico(s): Glycosylation and Glycoproteins Research
2020 - National Academy of Sciences | Proceedings of the National Academy of Sciences
Daniel A. Cannon, Lu Shan, Qun Du, Lena Shirinian, Keith Rickert, Kim L. Rosenthal, Martin Korade, Lilian E. van Vlerken-Ysla, Andrew Buchanan, Tristan J. Vaughan, Melissa Damschroder, Bojana Popovic,
Antibodies are an important class of therapeutics that have significant clinical impact for the treatment of severe diseases. Computational tools to support antibody drug discovery have been developing at an increasing rate over the last decade and typically rely upon a predetermined co-crystal structure of the antibody bound to the antigen for structural predictions. Here, we show an example of successful in silico affinity maturation of a hybridoma derived antibody, AB1, using just a homology ...
Tópico(s): Protein purification and stability
2019 - Public Library of Science | PLoS Computational Biology
Katherine A. Vousden, T. Lundqvist, Bojana Popovic, Brian Naiman, Alan Carruthers, Philip M. Newton, Daniel J. D. Johnson, Anja Pomowski, Trevor Wilkinson, Patrick Dufner, Isabelle de Mendez, Philip R. Mallinder, Clare Murray, Martin Strain, Jane R. Connor, Lynne A. Murray, Matthew A. Sleeman, David C. Lowe, James A. Huntington, Tristan J. Vaughan,
Abstract Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor (serpin) that regulates fibrinolysis, cell adhesion and cell motility via its interactions with plasminogen activators and vitronectin. PAI-1 has been shown to play a role in a number of diverse pathologies including cardiovascular diseases, obesity and cancer and is therefore an attractive therapeutic target. However the multiple patho-physiological roles of PAI-1, and understanding the relative contributions of these ...
Tópico(s): Blood Coagulation and Thrombosis Mechanisms
2019 - Nature Portfolio | Scientific Reports
Wendy A. Williams, John E. Linley, Clare A. Jones, Yoko Shibata, Arjan Snijder, James Button, Jon P. Hatcher, Ling Huang, Bruck Taddese, Peter Thornton, Darren J. Schofield, George Thom, Bojana Popovic, Bhupinder Dosanjh, Trevor Wilkinson, Jane Hughes, Claire Dobson, Maria Groves, Carl I. Webster, Andy Billinton, Tristan J. Vaughan, Iain P. Chessell,
Abstract P2X4 is a ligand-gated ion channel implicated in neuropathic pain. Drug discovery efforts targeting P2X4 have been unsuccessful largely because of the difficulty in engineering specificity and selectivity. Here, we describe for the first time the generation of a panel of diverse monoclonal antibodies (mAbs) to human and mouse P2X4, capable of both positive and negative modulation of channel function. The affinity-optimised anti-P2X4 mAb IgG#151-LO showed exquisite selectivity for human P2X4 ...
Tópico(s): Neuropeptides and Animal Physiology
2019 - Lippincott Williams & Wilkins | Pain
Bojana Popović, Dejana Popović, Djuro Macut, Ivana Božić Antić, Tatjana Isailović, Sanja Ognjanović, Tamara Bogavac, Valentina Elezović Kovačević, Dušan Ilić, M. Petrovic, Svetozar Damjanović,
Endocrine system plays a major role in both permissive and regulatory activities in order to adequately respond to physical stress of exercise. But level and direction of activation depend on many factors and are not easily interpreted.We tested a group of male professional athletes (21 water polo players and 15 wrestlers), together with 20 sedentary controls matched by age. All participants took a continuous progressive exercise stress test on a treadmill until exhaustion and plateau of oxygen consumption ( ...
Tópico(s): Exercise and Physiological Responses
2018 - De Gruyter | Journal of Medical Biochemistry
Caroline Colley, Bojana Popovic, Sudharsan Sridharan, J.E. Debreczeni, David Hargeaves, Michael Fung, Ling–Ling An, Bryan Edwards, Joanne Arnold, Elizabeth England, Laura Eghobamien, Ulf Sivars, Liz Flavell, Jonathan Renshaw, Kate F. Wickson, Paul Warrener, Jingying Zha, Jessica Bonnell, Rob Woods, Trevor Wilkinson, Claire Dobson, Tristan J. Vaughan,
C5a is a potent anaphylatoxin that modulates inflammation through the C5aR1 and C5aR2 receptors. The molecular interactions between C5a-C5aR1 receptor are well defined, whereas C5a-C5aR2 receptor interactions are poorly understood. Here, we describe the generation of a human antibody, MEDI7814, that neutralizes C5a and C5adesArg binding to the C5aR1 and C5aR2 receptors, without affecting complement-mediated bacterial cell killing. Unlike other anti-C5a mAbs described, this antibody has been shown ...
Tópico(s): Complement system in diseases
2017 - Landes Bioscience | mAbs
Pietro Sormanni, Leanne Amery, Sofia Ekizoglou, Michele Vendruscolo, Bojana Popovic,
Antibodies represent essential tools in research and diagnostics and are rapidly growing in importance as therapeutics. Commonly used methods to obtain novel antibodies typically yield several candidates capable of engaging a given target. The development steps that follow, however, are usually performed with only one or few candidates since they can be resource demanding, thereby increasing the risk of failure of the overall antibody discovery program. In particular, insufficient solubility, which ...
Tópico(s): Viral Infectious Diseases and Gene Expression in Insects
2017 - Nature Portfolio | Scientific Reports
Cristian Regep, Guy Georges, Jiye Shi, Bojana Popovic, Charlotte M. Deane,
The H3 loop in the Complementarity Determining Region of antibodies plays a key role in their ability to bind the diverse space of potential antigens. It is also exceptionally difficult to model computationally causing a significant hurdle for in silico development of antibody biotherapeutics. In this article, we show that most H3s have unique structural characteristics which may explain why they are so challenging to model. We found that over 75% of H3 loops do not have a sub-Angstrom structural ...
Tópico(s): Glycosylation and Glycoproteins Research
2017 - Wiley | Proteins Structure Function and Bioinformatics
Hiroki Shirai, Catherine Prades, Randi Vita, Paolo Marcatili, Bojana Popovic, Jianqing Xu, John P. Overington, Kazunori Hirayama, Shinji Soga, Kazuhisa Tsunoyama, Dominic A. Clark, Marie‐Paule Lefranc, Kazuyoshi Ikeda,
Tópico(s): vaccines and immunoinformatics approaches
2014 - Elsevier BV | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Produção Nacional
Revisado por pares
Andrew Buchanan, Veronica Clementel, Rob Woods, Nicholas Harn, Michael A. Bowen, Wenjun Mo, Bojana Popovic, Steven M. Bishop, William F. Dall’Acqua, Ralph Minter, Lutz Jermutus, Vahe Bedian,
Antibodies can undergo a variety of covalent and non-covalent degradation reactions that have adverse effects on efficacy, safety, manufacture and storage. We had identified an antibody to Angiopoietin 2 (Ang2 mAb) that neutralizes Ang2 binding to its receptor in vitro and inhibits tumor growth in vivo. Despite favorable pharmacological activity, the Ang2 mAb preparations were heterogeneous, aggregated rapidly and were poorly expressed. Here, we report the engineering of the antibody variable and ...
Tópico(s): Protein purification and stability
2013 - Landes Bioscience | mAbs
Svetozar Damjanović, Jadranka Antić, Bojana Ilic, Bojana Beleslin Čokić, Miomira Ivović, Sanja Ognjanović, Tatjana Isailović, Bojana Popović, Ivana Božić Antić, Svetislav Tatić, Gordana Matić, Vera Todorović, Ivan Paunović,
Glucocorticoid (GC) sensitivity depends on glucocorticoid receptor (GR) and heat shock proteins (Hsps). We investigated whether common GR genes (ER22/23EK N363S, Bcl I, and 9β) and adrenocorticotropin receptor promoter polymorphisms influence susceptibility for unilateral adrenal incidentaloma (AI), plus GR and Hsp expression in tumorous (n = 19), peritumorous (n = 13) and normal adrenocortical (n = 11) tissues. Patients (n = 112), population-matched controls (n = 100) and tumor tissues (n = 32) were genotyped for these ...
Tópico(s): Adrenal Hormones and Disorders
2012 - BioMed Central | Molecular Medicine
David C. Lowe, S. Gerhardt, Alison Ward, David Hargreaves, Malcolm Anderson, Franco Ferraro, Richard A. Pauptit, Debbie V. Pattison, Catriona L. Buchanan, Bojana Popovic, Donna K. Finch, Trevor Wilkinson, Matthew A. Sleeman, Tristan J. Vaughan, Philip R. Mallinder,
Interleukin (IL) 15 is an inflammatory cytokine that plays an essential role in the activation, proliferation, and maintenance of specific natural killer cell and T-cell populations, and has been implicated as a mediator of inflammatory diseases. An anti-IL-15 antibody that blocked IL-15-dependent cellular responses was isolated by phage display and optimised via mutagenesis of the third complementarity-determining regions (CDRs) of variable heavy (VH) and variable light chains. Entire repertoires ...
Tópico(s): T-cell and B-cell Immunology
2010 - Elsevier BV | Journal of Molecular Biology
Svetozar Damjanović, Rada V. Stojic, Nebojša Lalić, Aleksandra Jotić, Djuro Macut, Sanja Ognjanović, Мilan Petakov, Bojana Popović,
Tópico(s): Growth Hormone and Insulin-like Growth Factors
2009 - Springer Science+Business Media | Endocrine
S. Gerhardt, W. Mark Abbott, David Hargreaves, Richard A. Pauptit, Rick A. Davies, M. Needham, Caroline Langham, Wendy Barker, Azad Aziz, Melanie J. Snow, Sarah Dawson, Fraser Welsh, Trevor Wilkinson, Tris Vaugan, Gerald Beste, Sarah A. Bishop, Bojana Popovic, Gareth Rees, Matthew A. Sleeman, Steven Tuske, Stephen J. Coales, Yoshitomo Hamuro, CAROLINE S. RUSSELL,
IL-17A is a pro-inflammatory cytokine produced by the newly identified Th17 subset of T-cells. We have isolated a human monoclonal antibody to IL-17A (CAT-2200) that can potently neutralize the effects of recombinant and native human IL-17A. We determined the crystal structure of IL-17A in complex with the CAT-2200 Fab at 2.6 Å resolution in order to provide a definitive characterization of the epitope and paratope regions. Approximately a third of the IL-17A dimer is disordered in this crystal structure. ...
Tópico(s): Monoclonal and Polyclonal Antibodies Research
2009 - Elsevier BV | Journal of Molecular Biology
David H. Kwan, Yuhui Sun, Frank Schulz, Hui Hong, Bojana Popovic, Joalice C.C. Sim-Stark, Stephen Haydock, Peter F. Leadlay,
When an enoylreductase enzyme of a modular polyketide synthase reduces a propionate extender unit that has been newly added to the growing polyketide chain, the resulting methyl branch may have either S or R configuration. We have uncovered a correlation between the presence or absence of a unique tyrosine residue in the ER active site and the chirality of the methyl branch that is introduced. When this position in the active site is occupied by a tyrosine residue, the methyl branch has S configuration, ...
Tópico(s): Plant-Microbe Interactions and Immunity
2008 - Elsevier BV | Chemistry & Biology
Abel Baerga‐Ortiz, Bojana Popovic, Alexandros Siskos, Helen M. O’Hare, Dieter Spiteller, Mark Williams, Nuria E. Campillo, Jonathan B. Spencer, Peter F. Leadlay,
Tópico(s): Genomics and Phylogenetic Studies
2006 - Elsevier BV | Chemistry & Biology
Bojana Popovic, Xiao Tang, Dimitri Y. Chirgadze, Fanglu Huang, Tom L. Blundell, Jonathan B. Spencer,
Abstract The aminotransferase (BtrR), which is involved in the biosynthesis of butirosin, a 2‐deoxystreptamine (2‐DOS)‐containing aminoglycoside antibiotic produced by Bacillus circulans, catalyses the pyridoxal phosphate (PLP)‐dependent transamination reaction both of 2‐deoxy‐ scyllo ‐inosose to 2‐deoxy‐ scyllo ‐inosamine and of amino‐dideoxy‐ scyllo ‐inosose to 2‐DOS. The high‐resolution crystal structures of the PLP‐ and PMP‐bound forms of BtrR aminotransferase from B. circulans were solved at resolutions ...
Tópico(s): Genomics and Phylogenetic Studies
2006 - Wiley | Proteins Structure Function and Bioinformatics
Kira J. Weissman, Hui Hong, Bojana Popovic, Filip Meersman,
During biosynthesis on modular polyketide synthases (PKSs), chain extension intermediates are tethered to acyl carrier protein (ACP) domains through phosphopantetheinyl prosthetic groups. Each ACP must therefore interact with every other domain within the module, and also with a downstream acceptor domain. The nature of these interactions is key to our understanding of the topology and operation of these multienzymes. Sequence analysis and homology modeling implicates a potential helical region (helix ...
Tópico(s): Carbohydrate Chemistry and Synthesis
2006 - Elsevier BV | Chemistry & Biology
Helen M. O’Hare, Abel Baerga‐Ortiz, Bojana Popovic, Jonathan B. Spencer, Peter F. Leadlay,
Ketoreductase (KR) activities help determine the stereochemistry of the products of modular polyketide synthases (PKSs). For example, domains eryKR(1) and eryKR(2), contained, respectively, in the first and second extension modules of the erythromycin-producing PKS, reduce 3-ketoacyl-thioester intermediates with opposite stereospecificity. Amino acid motifs that correlate with stereochemical outcome have been identified in KRs. We have used saturation mutagenesis of these motifs in eryKR(1) and eryKR( ...
Tópico(s): Enzyme Catalysis and Immobilization
2006 - Elsevier BV | Chemistry & Biology
Alexandros Siskos, Abel Baerga‐Ortiz, Shilpa Bali, Viktor Stein, Hassan Mamdani, Dieter Spiteller, Bojana Popovic, Jonathan B. Spencer, James Staunton, Kira J. Weissman, Peter F. Leadlay,
A system is reported for the recombinant expression of individual ketoreductase (KR) domains from modular polyketide synthases (PKSs) and scrutiny of their intrinsic specificity and stereospecificity toward surrogate diketide substrates. The eryKR1 and the tylKR1 domains, derived from the first extension module of the erythromycin PKS and the tylosin PKS, respectively, both catalyzed reduction of (2R, S)-2-methyl-3-oxopentanoic acid N-acetylcysteamine thioester, with complete stereoselectivity and ...
Tópico(s): Enzyme Production and Characterization
2005 - Elsevier BV | Chemistry & Biology
S. Pavlović, Vera Artiko, Dragana Šobić-Šaranović, Svetozar Damjanović, Bojana Popović, Radoslav Jaković, Zorica Petrasinovic, Emilija Jakšić, Mila Todorovic‐Tirnanic, Dj. Saranovic, Marjan Micev, Sunčica Andreja Novosel, Neda Nikolić, Vladimir Obradović,
Our aim was to assess clinical utility of 99m Tc-EDDA/HYNIC-TOC scintigraphy for evaluation of lung lesions in patients with neuroendocrine tumors (NETs).Single photon emission computed tomography (SPECT) of the thorax and whole body scintigraphy were performed in 34 patients using 99m Tc-EDDA/HYNIC-TOC.Visual assessment was complemented by semiquantitative evaluation based on tumor to non-tumor (T/NT) ratio.Clinical, laboratory, and histological findings served as the standard for comparison.Enhanced ...
Tópico(s): Gyrotron and Vacuum Electronics Research
2010 - AEPress | Neoplasma
Dejana Popović, Miodrag Ostojić, M Petrović, B. Vujisic-Tesic, Bojana Popović, Ivana Nedeljković, Aleksandra Arandjelovic, Branko Jakovljević, Vesna Stojanov, Svetozar Damjanović,
Since diastolic dysfunction is an early sign of the heart disease, detecting diastolic disturbances is predicted to be the way for early recognizing underlying heart disease in athletes. So‐called chamber stiffness index (E/e′)/LVDd was predicted to be useful in distinguishing physiological from pathological left ventricular hypertrophy, because it was shown to be reduced in athletes. It remains unknown whether it is reduced in all athletic population. Standard and tissue Doppler were used to assess ...
Tópico(s): Cardiovascular and exercise physiology
2010 - Wiley | Echocardiography
David Bannister, Bojana Popovic, Sridha Sridharan, F. Giannotta, Patrice Filée, Nursel Yilmaz, Ralph Minter,
Monoclonal antibodies are a commercially successful class of drug molecules and there are now a growing number of antibodies coupled to toxic payloads, which demonstrate clinical efficacy. Determining the precise epitope of therapeutic antibodies is beneficial in understanding the structure–activity relationship of the drug, but in many cases is not done due to the structural complexity of, in particular, conformational protein epitopes. Using the immunotoxin CAT-8015 as a test case, this study ...
Tópico(s): Bacteriophages and microbial interactions
2010 - Oxford University Press | Protein Engineering Design and Selection
Bojana Popovic, Suzanne J. Gibson, Tarik Senussi, Sara Carmen, Sara Kidd, Tim Slidel, Ian Strickland, Jianqing Xu, Jennifer Spooner, Amanda L. Lewis, Nathan E. Hudson, Lorna Mackenzie, Jennifer Keen, Benjamin Kemp, Colin Hardman, Diane Hatton, Trevor Wilkinson, Tristan J. Vaughan, David C. Lowe,
High levels of protein expression are key to the successful development and manufacture of a therapeutic antibody. Here, we describe two related antibodies, Ab001 and Ab008, where Ab001 shows a markedly lower level of expression relative to Ab008 when stably expressed in Chinese hamster ovary cells. We use single-gene expression vectors and structural analysis to show that the reduced titer is associated with the VL CDR2 of Ab001. We adopted two approaches to improve the expression of Ab001. First, ...
Tópico(s): Transgenic Plants and Applications
2017 - Oxford University Press | Protein Engineering Design and Selection