7 results on '"János Szolomajer"'
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2. Potent Chimeric Antimicrobial Derivatives of the Medicago truncatula NCR247 Symbiotic Peptide
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Sándor Jenei, Hilda Tiricz, János Szolomájer, Edit Tímár, Éva Klement, Mohamad Anas Al Bouni, Rui M. Lima, Diána Kata, Mária Harmati, Krisztina Buzás, Imre Földesi, Gábor K. Tóth, Gabriella Endre, and Éva Kondorosi
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antimicrobial peptides ,plant symbiotic nodule-specific cysteine-rich peptides ,NCR247 ,ESKAPE bacteria ,modes of antimicrobial activity ,killing kinetics ,Microbiology ,QR1-502 - Abstract
In Rhizobium-legume symbiosis, the bacteria are converted into nitrogen-fixing bacteroids. In many legume species, differentiation of the endosymbiotic bacteria is irreversible, culminating in definitive loss of their cell division ability. This terminal differentiation is mediated by plant peptides produced in the symbiotic cells. In Medicago truncatula more than ∼700 nodule-specific cysteine-rich (NCR) peptides are involved in this process. We have shown previously that NCR247 and NCR335 have strong antimicrobial activity on various pathogenic bacteria and identified interaction of NCR247 with many bacterial proteins, including FtsZ and several ribosomal proteins, which prevent bacterial cell division and protein synthesis. In this study we designed and synthetized various derivatives of NCR247, including shorter fragments and various chimeric derivatives. The antimicrobial activity of these peptides was tested on the ESKAPE bacteria; Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli as a member of Enterobacteriaceae and in addition Listeria monocytogenes and Salmonella enterica. The 12 amino acid long C-terminal half of NCR247, NCR247C partially retained the antimicrobial activity and preserved the multitarget interactions with partners of NCR247. Nevertheless NCR247C became ineffective on S. aureus, P. aeruginosa, and L. monocytogenes. The chimeric derivatives obtained by fusion of NCR247C with other peptide fragments and particularly with a truncated mastoparan sequence significantly increased bactericidal activity and altered the antimicrobial spectrum. The minimal bactericidal concentration of the most potent derivatives was 1.6 μM, which is remarkably lower than that of most classical antibiotics. The killing activity of the NCR247-based chimeric peptides was practically instant. Importantly, these peptides had no hemolytic activity or cytotoxicity on human cells. The properties of these NCR derivatives make them promising antimicrobials for clinical use.
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- 2020
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3. Electrospray Ionization Mass Spectrometric Analysis of Highly Reactive Glycosyl Halides
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Lajos Kovács, János Szolomájer, Tünde Zita Illyés, Zoltán Kele, Attila Bokros, Annamária Bánfi, and Zoltán Kupihár
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glycosyl halides ,electrospray mass spectrometry ,nanoelectrospray ,lithium salts ,Organic chemistry ,QD241-441 - Abstract
Highly reactive glycosyl chlorides and bromides have been analysed by a routine mass spectrometric method using electrospray ionization and lithium salt adduct-forming agents in anhydrous acetonitrile solution, providing salient lithiated molecular ions [M+Li]+, [2M+Li]+ etc. The role of other adduct-forming salts has also been evaluated. The lithium salt method is useful for accurate mass determination of these highly sensitive compounds.
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- 2012
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4. Enhanced Antibacterial Activity of Substituted Derivatives of NCR169C Peptide
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Dian H. O. Howan, Sándor Jenei, János Szolomajer, Gabriella Endre, Éva Kondorosi, and Gábor K. Tóth
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antimicrobial resistance ,antimicrobial peptides ,Medicago truncatula ,nodule-specific cysteine-rich ,modified trytophans ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Medicago truncatula in symbiosis with its rhizobial bacterium partner produces more than 700 nodule-specific cysteine-rich (NCR) peptides with diverse physicochemical properties. Most of the cationic NCR peptides have antimicrobial activity and the potential to tackle antimicrobial resistance with their novel modes of action. This work focuses on the antibacterial activity of the NCR169 peptide derivatives as we previously demonstrated that the C-terminal sequence of NCR169 (NCR169C17–38) has antifungal activity, affecting the viability, morphology, and biofilm formation of various Candida species. Here, we show that NCR169C17–38 and its various substituted derivatives are also able to kill ESKAPE pathogens such as Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli. The replacement of the two cysteines with serines enhanced the antimicrobial activity against most of the tested bacteria, indicating that the formation of a disulfide bridge is not required. As tryptophan can play role in the interaction with bacterial membranes and thus in antibacterial activity, we replaced the tryptophans in the NCR169C17–38C12,17/S sequence with various modified tryptophans, namely 5-methyl tryptophan, 5-fluoro tryptophan, 6-fluoro tryptophan, 7-aza tryptophan, and 5-methoxy tryptophan, in the synthesis of NCR169C17–38C12,17/S analogs. The results demonstrate that the presence of modified fluorotryptophans can significantly enhance the antimicrobial activity without notable hemolytic effect, and this finding could be beneficial for the further development of new AMPs from the members of the NCR peptide family.
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- 2023
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5. Symbiotic NCR Peptide Fragments Affect the Viability, Morphology and Biofilm Formation of Candida Species
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Bettina Szerencsés, Attila Gácser, Gabriella Endre, Ildikó Domonkos, Hilda Tiricz, Csaba Vágvölgyi, János Szolomajer, Dian H. O. Howan, Gábor K. Tóth, Ilona Pfeiffer, and Éva Kondorosi
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NCR peptide ,antifungal activity ,Candida ,morphological switch ,biofilm ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The increasing rate of fungal infections causes global problems not only in human healthcare but agriculture as well. To combat fungal pathogens limited numbers of antifungal agents are available therefore alternative drugs are needed. Antimicrobial peptides are potent candidates because of their broad activity spectrum and their diverse mode of actions. The model legume Medicago truncatula produces >700 nodule specific cysteine-rich (NCR) peptides in symbiosis and many of them have in vitro antimicrobial activities without considerable toxicity on human cells. In this work we demonstrate the anticandidal activity of the NCR335 and NCR169 peptide derivatives against five Candida species by using the micro-dilution method, measuring inhibition of biofilm formation with the XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) assay, and assessing the morphological change of dimorphic Candida species by microscopy. We show that both the N- and C-terminal regions of NCR335 possess anticandidal activity as well as the C-terminal sequence of NCR169. The active peptides inhibit biofilm formation and the yeast-hypha transformation. Combined treatment of C. auris with peptides and fluconazole revealed synergistic interactions and reduced 2-8-fold the minimal inhibitory concentrations. Our results demonstrate that shortening NCR peptides can even enhance and broaden their anticandidal activity and therapeutic potential.
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- 2021
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6. Synthesis of the extracellular domain of GLP-1R by chemical and biotechnological approaches
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János Szolomajer, Pál Stráner, Zoltán Kele, Gábor K. Tóth, and András Perczel
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General Chemical Engineering ,01.04. Kémiai tudományok ,General Chemistry - Abstract
The extracellular domain of the glucagon-like peptide-1 receptor, GLP-1R, is responsible for the binding of GLP-1, and a handful of additional agonists (such as exenatide, lixisenatide, and liraglutide) used daily for treating type II diabetes mellitus. Lead discovery and optimization, however, require binding studies, which, in turn, necessitate the total synthesis of GLP-1R, comprising 108 residues. A protein domain of 10–15 kDa size could be obtained either by expression in E. coli or by ligating solid-phase peptide synthesis (SPPS)-made fragments. However, direct overexpression fails to give a properly folded protein, as GLP-1R forms an inclusion body, which fails to refold due to improper disulfide pairing. Several bacterial strains, constructs, and fusion partners were probed and it was found that only co-expression with MBP gave a 3D-fold allowing the native disulfide bond pattern formation. Some fusion partners can act as covalently linked or in situ chaperones for guiding the refolding of GLP-1R toward success. Therefore, the bottleneck to preparing GPCR extracellular domains is the correct pairing of the Cys residues. As a proof-of-concept model, nGLP1-R was made by SPPS to form the purified full-length polypeptide chain, subjected to self-guided or spontaneous Cys pairing. However, the formation of correct SS-pairs was lagging behind any protocol in use support, and the bottleneck of large-scale protein production relies on the risky step of proper refolding, which is sometimes possible only if a suitable fusion partner effectively helps and catalysis of the correct disulfide formation.
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- 2022
7. Proline cis/trans Isomerization in Intrinsically Disordered Proteins and Peptides
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Fanni Sebák, János Szolomájer, Nándor Papp, Gábor K. Tóth, and Andrea Bodor
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intrinsically disordered proteins ,nmr spectroscopy ,proline ,cis/trans isomerization ,statistical analysis ,Biochemistry ,QD415-436 ,Biology (General) ,QH301-705.5 - Abstract
Background: Intrinsically disordered proteins and protein regions (IDPs/IDRs) are important in diverse biological processes. Lacking a stable secondary structure, they display an ensemble of conformations. One factor contributing to this conformational heterogeneity is the proline cis/trans isomerization. The knowledge and value of a given cis/trans proline ratio are paramount, as the different conformational states can be responsible for different biological functions. Nuclear Magnetic Resonance (NMR) spectroscopy is the only method to characterize the two co-existing isomers on an atomic level, and only a few works report on these data. Methods: After collecting the available experimental literature findings, we conducted a statistical analysis regarding the influence of the neighboring amino acid types (i ± 4 regions) on forming a cis-Pro isomer. Based on this, several regularities were formulated. NMR spectroscopy was then used to define the cis-Pro content on model peptides and desired point mutations. Results: Analysis of NMR spectra prove the dependence of the cis-Pro content on the type of the neighboring amino acid—with special attention on aromatic and positively charged sidechains. Conclusions: Our results may benefit the design of protein regions with a given cis-Pro content, and contribute to a better understanding of the roles and functions of IDPs.
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- 2023
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