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The paper deals with the material analysis of four emblematic stone fragments from Saint Adalbert Cathedral and the Royal Palace of Esztergom from King Béla III’s era. All of the four examined objects (two fragments from the Porta speciosa and two throne arm-rests) have incrustations with red limestone basement and other colourful stone pieces. As red limestone is a well-known material in Hungarian art history with a rich historiography, the paper focuses on the findings of the analyses of other stone materials of the incrustations. The research contains several non-destructive analytical methods, such as relative humidity measurement, macroscopic and microscopic photography and X-ray fluorescence with lithologic description. Besides the comparative analysis of the stone materials, archive documents, the current state and the impacts of subsequent restorations of the four stone artefacts were also studied.

Gothic architecture can be viewed from several perspectives, including stylistic aspects, architectural theory, and structural analysis.As Gothic architecture is a skeletal construction, it is essential to achieve an equilibrium with the multiple loads and forces. Medieval master masons' architectural knowledge was firmly based on empirical learning, which stimulated the dynamic development of structural innovations.This paper emphasises and describes a particular type of vault springer, one of the most complicated and sensitive parts of Gothic construction. Known as tas-de-charge, it became especially characteristic of high Gothic architecture. According to its principle, the springer's lower courses contain the merged vault nerves and are carved from one single stone block in each course. The beds of these courses are not radial as those of the average voussoirs, but horizontal. Without the concept of tas-de-charge, the development of late Gothic vaults could not be imaginable. This particular solution made possible the creation of elegantly narrow imposts supporting the vault ribs, the double arch and the formerets. So far, tas-de-charge has not been a focus of interest in the historiography of Hungarian medieval architecture; however, it appears that it was commonly applied in our late Romanesque and early Gothic monuments.

A tanulmánysorozat szerzői bemutatták és elemezték a hagyományos meghajtású repülő eszközök alternatív energiahordozókkal történő lecserélésének okait és 21. századi lehetőségeit. Az olvasók megismerhették az elektromos és hibrid meghajtás technológiáit, valamint a pilóta nélküli repülőeszközök (UAV – Unmanned Aerial Vehicle) polgári és katonai célokra történő felhasználásának széleskörű példatárát. A sorozat záró része a magyar szerepvállalásra és a hazai ipari részvételre koncentrál. Kiemelt figyelem irányul a nemzetközi cégekkel kooperáló, hazánkban működő, legkorszerűbb technológiákat alkalmazó vállatokra és gyáregységekre.

A folyamatosan csökkenő mennyiségű hagyományos, fosszilis eredetű energiahordozók környezetkímélő kiváltására a légi közlekedésben jelenleg döntően az elektromos meghajtású repülőeszközök jöhetnek számításba. A tanulmány korábbi részeiben a szerzők áttekintették repülőeszközök működtetéséhez alkalmazott energiahordozók fajtáit, a környezetszennyezés csökkentése érdekében szóba jöhető alternatív energiaforrások kiválasztásának szempontjait, majd a repülés környezeti hatásait. Felvetették a dinamikusan növekvő légi forgalom és a környezetvédelemi szabályozás ellentmondásait, elemezték az alternatívenergia-bevezetés kényszerű lassulásának okait, valamint aggályokat fogalmaztak meg a 2050-ig tartó fejlődés lehetőségeiről. A tanulmány bemutatta a katonai repülés és a környezetszennyezés arányait, majd a nemzetközi társadalmi, politikai, katonai válságok, illetve a koronavírus-járvány hatásait vizsgálta a repülőiparra és a légi közlekedésre. Ezt követően önálló rész foglalkozott az elektromos meghajtású repülőeszközök gyors bevezetésének kényszerhelyzetével, valamint az azzal járó kompromisszumokkal. A sorozat IV. része előbb az akkumulátoros energiatárolás, majd a villamos meghajtás legfőbb nehézségeit mutatja be. A szerzők az UAV-k különböző típusain az adott eszközök előnyeit és hátrányait emelik ki. Ezt követően az érdeklődők a napelemes légi utántöltéssel, az új típusú akkumulátorokkal, valamint az üzemanyagcellák alkalmazásának egyes változataival ismerkedhetnek meg.

BACKGROUND: Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. METHODS: AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (

Human galectin-3 (

Napjaink egyik legnagyobb technikai kihívása az egyre csökkenő mennyiségben kitermelhető hagyományos, fosszilis eredetű energiahordozók kiváltása, pótlása. Bár a légi közlekedésben erre megnyugtató, hosszú távú megoldás még nem született, századunk ’50-es éveire a túlnépesedett Föld akkori lakóinak kétharmadát befogadó metropoliszokban elkerülhetetlen a harmadik dimenzió bevonása a közlekedésbe, kizárólag karbonmentes módon. Erre jelenleg csak az elektromos meghajtású repülőeszközök jöhetnek számításba, amelyek ezirányú fejlesztése már tart, és a projektet az USAF (United States Air Force – Egyesült Államok Légiereje) is támogatja.

Since the 19th century, the church of Zsámbék was continuously a focus of scholars' interest. The present paper intends to research the church ruins with a new aspect. Using an accurate terrestrial laser scan survey, the geometry of the plan is analysed in order to find proportions among the dimensions. The main goal of the study is to gather information about the design logic of the first masters of the 13th-century Premonstratensian abbey. In addition, our goal was to detect contributions to the 13th-century construction history of the church, that cannot be found in archives of graphic sources. The latest archaeological excavation achieved excellent results concerning several crucial historical points; however, the periodization of the church is still not entirely clarified. From the 19th century, different scholars have proposed various hypotheses about this topic, without consensus.

A range of entirely different pentagon approximations are known from textual and graphic sources related to the architecture of the Middle Ages. Analysis of the mathematical logic behind them highlights the scientific knowledge of master masons who directly calculated constructional methods according to their practical needs. From the examination of these pentagon approximations, their mathematical features, such as the initial data of the construction or precision of side lengths and angles, the range of architectural design problems they would have been able to solve can be determined. This paper provides an accurate comparison of mathematical and geometrical features of pentagon constructions from medieval sources, studying their applicability from an architectural aspect.

A két világháború közötti magyar építészeti közélet egyik legnagyobb hatású eseménye az 1930-ban Budapesten rendezett XII. Nemzetközi Építészkongresszus volt. A kongresszus programjához kapcsolódóan a Műcsarnokban nemzetközi tervkiállítást, a Műegyetemen pedig hallgatói tervekből készült kiállítást rendeztek. Ez utóbbinak érthető módon eltörpül a sajtóbeli visszhangja a másikhoz képest, az Építészettörténeti és Műemléki Tanszék rajztárának feldolgozásakor azonban egy olyan összefüggő tablósorozat került elő, amelynek egységes, öt nyelven feliratozott grafikája és keltezései is arra utalnak, hogy a Műegyetem kiállítási anyagához tartozhatott. A tablókra kasírozott építészettörténeti rajzok bizonyíthatják, és ekképpen majdhogynem az egyedüli bizonyítékai, hogy a Műegyetemen a tervezésoktatás mellett más tárgycsoportok, így az építészettörténet is bemutatásra került. A tablók fontos adalékot szolgáltatnak az építészettörténet oktatásának két világháború közötti változásairól, a kongresszus és a kiállítások sajtóba leszűrődött visszhangja pedig a 19. században még egységben lévő építészeti tervezés és építészettörténet tovább élő viszonyára utalnak.

Elucidation and improvement of the blood coagulant properties of heparin are the focus of intense research. In this study, we performed conformational analysis using nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations on the heparin pentasaccharide analogue idraparinux, its disulfonatomethyl analogue, which features a slightly improved blood coagulation property, and a trisulfonatomethyl analogue, in which the activity has been totally abolished. As the ring conformation of the G subunit has been suggested as a major determinant of the biological properties, we analyzed the sugar ring conformations and dynamics of the interglycosidic linkages. We found that the conformation of the G ring is dominated by the 2SO skewed boat next to the 1C4 chair in all three derivatives. Both the thermodynamics and the kinetics of the conformational states were found to be highly similar in the three derivatives. Molecular kinetic analysis showed that the 2SO skewed boat state of the G ring is equally favorable in the three analogues, resulting in similar 2SO populations. Also, the transition kinetics from the 1C4 chair to the 2SO skewed boat was found to be comparable in the derivatives, which indicates a similar energy barrier between the two states of the G subunit. We also identified a slower conformational transition between the dominant 4C1 chair and the boat conformations on the E subunit. Both G and E ring flips are also accompanied by changes along the interglycosidic linkages, which take place highly synchronously with the ring flips. These findings indicate that conformational plasticity of the G ring and the dominance of the 2SO skewed boat populations do not necessarily warrant the biological activity of the derivatives and hence the impact of other factors also needs to be considered.

Background: Pseudocysts being the most frequent local complications of acute pancreatitis (AP) have substantial effect on the disease course, hospitalization and quality of life of the patient. Our study aimed to understand the effects of pre-existing (OLD-P) and newly developed (NEW-P) pseudocysts on AP. Methods: Data were extracted from the Acute Pancreatitis Registry organized by the Hungarian Pancreatic Study Group (HPSG). 2275 of 2461 patients had uploaded information concerning pancreatic morphology assessed by imaging technique. Patients were divided into “no pseudocyst” (NO-P) group, “old pseudocyst” (OLD-P) group, or “newly developed pseudocyst” (NEW-P) groups. Results: The median time of new pseudocyst development was nine days from hospital admission and eleven days from the beginning of the abdominal pain. More NEW-P cases were severe (15.9% vs 4.7% in the NO-P group p < 0.001), with longer length of hospitalization (LoH) (median: 14 days versus 8 days, p < 0.001), and were associated with several changed laboratory parameters. OLD-P was associated with male gender (72.2% vs. 56.1%, p = 0.0014), alcoholic etiology (35.2% vs. 19.8% in the NO-P group), longer hospitalization (median: 10 days, p < 0.001), a previous episode of AP (p < 0.001), pre-existing diagnosis of chronic pancreatitis (CP) (p < 0.001), current smoking (p < 0.001), and increased alcohol consumption (unit/week) (p = 0.014). Conclusion: Most of the new pseudocysts develop within two weeks. Newly developing pseudocysts are associated with a more severe disease course and increased length of hospitalization. Pre-existing pseudocysts are associated with higher alcohol consumption and smoking. Because CP is more frequently associated with a pre-existing pseudocyst, these patients need closer attention after AP.

International audience; We present an in-depth investigation of the membrane interactions of peptidoglycan (PGN)-based immune adjuvants designed for lipid-based delivery systems using NMR spectroscopy. The derivatives contain a cargo peptidoglycan (PGN) dipeptide fragment and an adamantyl group, which serves as an anchor to the lipid bilayer. Furthermore, derivatives with a mannose group that can actively target cell surface receptors on immune cells are also studied. We showed that the targeting mannose group and the cargo PGN fragment are both available on the lipid bilayer surface, thereby enabling interactions with cognate receptors. We found that the nonmannosylated compounds are incorporated stronger into the lipid assemblies than the mannosylated ones, but the latter compounds penetrate deeper in the bilayer. This might be explained by stronger electrostatic interactions available for zwitterionic nonmannosylated derivatives as opposed to the compounds in which the charged N-terminus is capped by mannose groups. The higher incorporation efficiency of the nonmannosylated compounds correlated with a larger relative enhancement in immune stimulation activities upon lipid incorporation compared to that of the derivatives with the mannose group. The chirality of the adamantyl group also influenced the incorporation efficiency, which in turn correlated with membrane-associated conformations that affect possible intermolecular interactions with lipid molecules. These findings will help in improving the development of PGN-based immune adjuvants suitable for delivery in lipid nanoparticles.

A műegyetemi epiteszkepzes kialakulasa szorosan osszefonodik a magyarorszagi historizmus epiteszetenek terhoditasaval, kiteljesedesevel. Az első tervezest oktato tanszekek aszerint tagozodtak, hogy professzoraik melyik torteneti korszak (okor, kozepkor, ujkor) stilusaban valo tervezest oktattak. A historizmus epiteszeteről es a stilusban tervezes oktatasarol mar a szohasznalat miatt is az az altalanosan elfogadott kepzetunk, hogy a torteneti korok stilusjegyei azok, amelyek meghatarozzak a tervezest. A modern mozgalom eppen a felesleges kulsősegek halmozasa miatt hirdette a torteneti formak elveteset az epiteszeti tervezesben es a műegyetemi oktatasban egyarant. Az Epiteszettorteneti es Műemleki Tanszek Rajz- es Fototara (tovabbiakban Epiteszettorteneti Rajztar) szamos hallgatoi rajzot tartalmaz, amelyek atfogo kepet tudnak adni az intezmenyesult oktatas első szakaszatol kezdődően zajlo valtozasi folyamatokrol, amelyek nem csak az oktatasban, hanem azzal kolcsonhatasban a tervezesben is megmutatkoztak. A rajzokat szerkezeti szempontbol vizsgalva kiserletet teszunk arra, hogy attekintsuk az epiteszeti tervezes es szerkezeti gondolkodas viszonyanak valtozasat a 19. szazadtol a masodik vilaghaboruig terjedő időszakban.

Ernő Foerk (1868-1934) born 150 years ago has significant oeuvre in the field of monument preservation and architectural education. As professor, one of his achievements was the organisation of summer survey camps named as ‘szünidei felvételek’ (vacation records) which was also accessible in published form. In the year of 1917 under his supervision, his students have surveyed all the scored Ottoman monuments of Hungary. In the following year these survey drawings were published with a brief summary of the history of Ottoman architecture in the territory of Hungary. Our paper is to submit the general circumstances of the Ottoman survey program supervised by Ernő Foerk with its historical background and the analysis of the methodology of the survey by the example of the türbe of Pécs.

Among regular polygons, the pentagon is considered to be barely used in medieval architectural compositions, due to its odd spatial appearance and difficult method of construction. The pentagon, representing the number five has a rich semantic role in Christian symbolism. Even though the proper way of construction was already invented in the Antiquity, there is no evidence of medieval architects having been aware of this knowledge. Contemporary sources only show approximative construction methods. In the Middle Ages the form has been used in architectural elements such as window traceries, towers and apses. As opposed to the general opinion supposing that this polygon has rarely been used, numerous examples bear record that its application can be considered as rather common. Our paper attempts to give an overview of the different methods architects could have used for regular pentagon construction during the Middle Ages, and the ways of applying the form.

The construction of the regular pentagon has always meant a difficult geometrical exercise for architects during the Middle Ages. As the correct drafting was forgotten after the Antiquity, several methods for its approximation had been invented in medieval times. As Golden Ratio appears between several parts of the regular pentagon, the role of the Fibonacci sequence in these approximate constructions is to be examined. The pentagonal drawing in the sketchbook of Villard de Honnecourt calls our attention to a possible way how medieval architects could have applied simple numerical ratios for getting angles they needed. The approximation of 72°, for instance, is likely to have been crucial for this pentagonal construction, as well as the approximation of Golden Ratio that could have been achieved by neighbouring pairs from Fibonacci’s sequence.

The quest for the secret of geometric design methods and proportioning strategies of medieval master builders dates back to the middle of the 19th century. The improvement of surveying technologies allows adapting the advantages of laser-based instruments and computer aided analysis to the observation of this subject of revolving relevance. The subject of the paper research is to present the analysis of medieval architectural details from a geometrical point of view. In the current status of the research the paper focuses on the methodological aspects of the surveying process of gothic architectural fragments.

Model experiments under laboratory conditions were carried out to assess the accumulation tendency of Zr from a silica-zirconia core–shell nanoparticles, synthesised for the assay. Acute exposition tests were conducted with Daphnia magna and Danio rerio and the accumulation tendency of the nano and the molecular form was compared. Significant elevation of Zr was found in the tissue of the test organisms treated by the NP compared to the control, however, the retention of zebrafish was lower than that of the daphnids. Increased level of bioconcentration factor and the strong correlation of the redundancy analysis data suggest accumulation tendency in D. magna, yet long-term experiments are required to prove and further assess the environmental risk of food-chain bioconcentration. The BCF results were under the REACH limit for the D. rerio groups indicating the low short-term accumulation tendency of Zr from the NP. However, Zr level was significantly higher in zebrafish individuals originating from the SiO2@ZrO2 NP exposed treatments compared to the groups supplemented by the same concentration of ZrOCl2, which did not result in the elevation of Zr in fish tissue. The trace element homeostasis of D. rerio was not affected by the acute SiO2@ZrO2 NP exposition and no lethality occurred.

Analysing the original drawings of Frigyes Schulek’s Calvinist Reformed Church in Szeged from 1882 kept in the Plan Collection and Archives of the BME Department for History of Architecture and of Monuments, its design process of geometric proportioning method can be entirely reconstructed. The result of this analysis shows that the Historicism of Schulek was not merely the replication of stylistic patterns of Gothic art but also the application of Medieval architectural principals and ideas. In the case of the Calvinist Reformed Church in Szeged, the essence of the design ‘in style’ was inspired by the contradictions of the function and the position of the building beside the main theoretic recommendation of Protestant church architecture of the time (Eisenacher Regulativ). The purity of the interior required by the function was compensated by the complexity of the geometry. The analysis presented in the paper sheds light not only on Schulek’s approach to Medieval architecture but also the various leve

International audience; Self-assembly of peptides into supramolecular structures represents an active field of research with potential applications ranging from material science to medicine. Their study typically involves the application of a large toolbox of spectroscopic and imaging techniques. However, quite often, the structural aspects remain underexposed. Besides, molecular modeling of the self-assembly process is usually difficult to handle, since a vast conformational space has to be sampled. Here, we have used an approach that combines short molecular dynamics simulations for peptide dimerization and NMR restraints to build a model of the supramolecular structure from the dimeric units. Experimental NMR data notably provide crucial information about the conformation of the monomeric units, the supramolecular assembly dimensions, and the orientation of the individual peptides within the assembly. This in silico/in vitro mixed approach enables us to define accurate atomistic models of supramolecular structures of the bacterial cyclic lipodepsipeptide pseudodesmin A.

Computational description of conformational and dynamic properties of anticoagulant heparin analogue pentasaccharides is of crucial importance in understanding their biological activities. We designed and synthesized idraparinux derivatives modified with sulfonatomethyl moieties at the D, F, and H glucose units that display varied potencies depending on the exact nature of the substitution. In this report we examined the capability of molecular dynamics (MD) simulations to describe the conformational behavior of these novel idraparinux derivatives. We used Gaussian accelerated MD (GAMD) simulations on the parent compound, idraparinux, to choose the most suitable carbohydrate force field for these type of compounds. GAMD provided significant acceleration of conformational transitions compared to classical MD. We compared descriptors obtained from GAMD with NMR spectroscopic parameters related to geometrical descriptors such as scalar couplings and nuclear Overhauser effects (NOE) measured on idraparinux. We found that the experimental data of idraparinux is best reproduced by the CHARMM carbohydrate force field. Furthermore, we propose a torsion angle parameter for the sulfonato-methyl group, which was developed for the chosen CHARMM force field using quantum chemical calculations and validated by comparison with NMR data. The work lays down the foundation of using MD simulations to gain insight into the conformational properties of sulfonato-methyl group modified idraparinux derivatives and to understand their structure-activity relationship thus enabling rational design of further modifications.

Proline is often found as a turn inducer in peptide or protein domains. Exploitation of its restricted conformational freedom led to the development of the d-Pro-l-Pro (corresponding to (R)-Pro–(S)-Pro) segment as a “templating” unit, frequently used in the design of β-hairpin peptidomimetics, in which conformational stability is, however, inherently linked to the cis–trans isomerization of the prolyl amide bonds. In this context, the stereoelectronic properties of the CF 3 group can aid in conformational control. Herein, the impact of α-trifluoromethylated proline analogues is examined for the design of enhanced β-turn inducers. A theoretical conformational study permitted the dipeptide (R)-Pro–(R)-TfmOxa (TfmOxa: 2-trifluoromethyloxazolidine-2-carboxylic acid) to be selected as a template with an increased trans–cis rotational energy barrier. NMR spectroscopic analysis of the Ac-(R)-Pro–(R)-TfmOxa–(S)-Val-OtBu β-turn model, obtained through an original synthetic pathway, validated the prevalence of a major trans–trans conformer and indicated the presence of an internal hydrogen bond. Altogether, it was shown that the (R)-Pro–(R)-TfmOxa template fulfilled all crucial β-turn-inducer criteria.

Silica@zirconia core@shell oxide nanoparticles of approx. 50 nm diameter were developed in view of an application as a novel carrier with adjuvant activities for cancer vaccines. To this end, the aim was to cover the surface of the nanocarrier by potent single stranded DNA (ssDNA) type immune stimulators used in cancer vaccination. Prior to characterizing the binding of ssDNA to the nanocarrier surface, the adsorption of deoxynucleoside monophosphate building blocks (dNMPs) was studied. After optimization of conditions for synthesis, solvent exchange and surface modification, the effects and possible interference of several buffers, such as HEPES, PIPES, MOPS and MOPSO, were also investigated. Formation of a new compound was revealed by UV–VIS spectroscopy during the recording of zeta potential vs. pH titration curves in the presence of HEPES and PIPES buffer in the neutral-acidic pH region. We identified this new species as gold ions etched from the electrode of the zeta cuvette, stabilized by the buffers via chelation, which is then followed by their conversion into gold nanoparticles.

A biologically active peptide toxin containing four diselenide bonds was synthesized. The diselenide network and its dynamics were disclosed using a combined NMR and MD approach., Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin containing four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve potential therapeutic use of the toxin, we have designed a double substituted analog, [N17A/F32T]-AnTx, which showed comparable Kv1.3 affinity to the wild-type peptide, but also a 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chemical synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace, by chemical synthesis, all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly, the key pharmacological properties of the Sec-[N17A/F32T]-AnTx are retained since the peptide is functionally active. We also propose here a combined experimental and theoretical approach including NOE- and 77Se-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-[N17A/F32T]-AnTx. Using this combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed characterization of the conformational dynamics around each disulfide/diselenide bridge.

A műemleki helyreallitasok es az epiteszettorteneti kutatas komoly szakmai korultekintest, a tema tobb resztudomany szempontjabol tortenő vizsgalatat igenyli. A tervezesi es előkeszitesi folyamat nemcsak napjainkban, hanem a torteneti korokban is az epiteszeti alkotas kulcskerdesenek tekinthető, ezert ennek ismerete mind az epiteszettortenet, mind pedig a műemlekvedelmi tevekenyseg fontos adalekaul szolgal. Tanulmanyunk a kozepkori epuletek geometriai, aranyossagi rendszereinek, tervezesi, szerkesztesi modszereinek osszefoglalasara es kronologikus rendben tortenő bemutatasara vallalkozik a hazai szakirodalom alapjan. Ennek a temanak magyarorszagi kutatastortenete — a nemzetkozi szakirodalommal osszhangban — a 19. szazad kozepere nyulik vissza. Ez alatt a tobb mint masfel evszazad alatt az epiteszettorteneti kerdesekben relevans tudomanyok — epiteszet, műveszettortenet, regeszet, szobraszat — kepviselői elterő, de egytől egyig előremutato nezőpontokkal gazdagitva gyarapitottak ismereteinket a kozepkor terv...

Biocompatible inorganic nano- and microcarriers can be suitable candidates for protein delivery. This study demonstrates facile methods of functionalization by using nanoscale linker molecules to change the protein adsorption capacity of hydroxyapatite (HA) powder. The adsorption capacity of bovine serum albumin as a model protein has been studied with respect to the surface modifications. The selected linker molecules (lysine, arginine, and phosphoserine) can influence the adsorption capacity by changing the electrostatic nature of the HA surface. Qualitative and quantitative analyses of linker-molecule interactions with the HA surface have been performed by using NMR spectroscopy, zeta-potential measurements, X-ray photoelectron spectroscopy, and thermogravimetric analyses. Additionally, correlations to theoretical isotherm models have been calculated with respect to Langmuir and Freundlich isotherms. Lysine and arginine increased the protein adsorption, whereas phosphoserine reduced the protein adsorption. The results show that the adsorption capacity can be controlled with different functionalization, depending on the protein-carrier selections under consideration. The scientific knowledge acquired from this study can be applied in various biotechnological applications that involve biomolecule-inorganic material interfaces.

International audience; G protein-coupled receptors (GPCRs) play an important role in many cellular responses; as such, their mechanism of action is of utmost interest. To gain insight into the active conformation of GPCRs, the X-ray crystal structures of nanobody (Nb)-stabilized β2 -adrenergic receptor (β2 AR) have been reported. Nb80, in particular, is able to bind the intracellular G protein binding site of β2 AR and stabilize the receptor in an active conformation. Within Nb80, the complementarity-determining region 3 (CDR3) is responsible for most of the binding interactions. Hence, we hypothesized that peptidomimetics of the CDR3 loop might be sufficient for binding to the receptor, inhibiting the interaction of β2 AR with intracellular GPCR interacting proteins (e.g., G proteins). Based on previous crystallographic data, a set of peptidomimetics were synthesized that, similar to the Nb80 CDR3 loop, adopt a β-hairpin conformation. Syntheses, conformational analysis, binding and functional in vitro assays, as well as internalization experiments, were performed. We demonstrate that peptidomimetics can structurally mimic the CDR3 loop of a nanobody and its function by inhibiting G protein coupling as measured by partial inhibition of cAMP production.

G protein-coupled receptors (GPCRs) play an important role in many cellular responses; as such, their mechanism of action is of utmost interest. To gain insight into the active conformation of GPCRs, the X-ray crystal structures of nanobody (Nb)-stabilized β

Many Pseudomonas spp. produce cyclic lipodepsipeptides (CLPs), which, besides their role in biological functions such as motility, biofilm formation and interspecies interactions, are antimicrobial. It has been established that interaction with the cellular membrane is central to the mode of action of CLPs. In this work, we focus on the CLPs of the so-called viscosin group, aiming to assess the impact of the main structural variations observed within this group on both the antimicrobial activity and the interaction with model membranes. The antimicrobial activity of viscosin, viscosinamide A, WLIP and pseudodesmin A were all tested on a broad panel of mainly Gram-positive bacteria. Their capacity to permeabilize or fuse PG/PE/cardiolipin model membrane vesicles is assessed using fluorescent probes. We find that the Glu2/Gln2 structural variation within the viscosin group is the main factor that influences both the membrane permeabilization properties and the minimum inhibitory concentration of bacterial growth, while the configuration of the Leu5 residue has no apparent effect. The CLP-membrane interactions were further evaluated using CD and FT-IR spectroscopy on model membranes consisting of PG/PE/cardiolipin or POPC with or without cholesterol. In contrast to previous studies, we observe no conformational change upon membrane insertion. The CLPs interact both with the polar heads and aliphatic tails of model membrane systems, altering bilayer fluidity, while cholesterol reduces CLP insertion depth.

To address the need for highly potent, metabolically stable, and selective agonists, antagonists, and inverse agonists at the melanocortin receptor subtypes, conformationally constrained indolo- and benzazepinone residues were inserted into the α-MSH pharmacophore, His(6)-Phe(7)-Arg(8)-Trp(9)-domain. Replacement of His(6) by an aminoindoloazepinone (Aia) or aminobenzazepinone (Aba) moiety led to hMC4R and hMC5R selective agonist and antagonist ligands, respectively (tetrapeptides 1 to 3 and 4, respectively). In peptides 1 to 3 and depending on the para-substituent of the d-Phe residue in position 2, the activity goes from allosteric partial agonism (1, R = H) to allosteric full agonism (2, R = F) and finally allosteric partial agonism (3, R = Br).

The predictable 3D structure of double-stranded DNA renders it ideally suited as a template for the bottom-up design of functionalized nucleic acid-based active sites. We here explore the use of a 14mer DNA duplex as a scaffold for the precise and predictable positioning of catalytic functionalities. Given the ubiquitous participation of the histidine-based imidazole group in protein recognition and catalysis events, single histidine-like modified duplexes were investigated. Tethering histamine to the C5 of the thymine base via an amide bond, allows the flexible positioning of the imidazole function in the major groove. The mutual interactions between the imidazole and the duplex and its influence on the imidazolium pKa(H) are investigated by placing a single modified thymine at four different positions in the center of the 14mer double helix. Using NMR and unrestrained molecular dynamics, a structural motif involving the formation of a hydrogen bond between the imidazole and the Hoogsteen side of the guanine bases of two neighboring GC base pairs is established. The motif contributes to a stabilization against thermal melting of 6 degrees C and is key in modulating the pKa(H) of the imidazolium group. The general features, prerequisites and generic character of the new pKa(H)-regulating motif are described.

We report an efficient and adaptable method for the microencapsulation of active ingredients by a polydimethylsiloxane (PDMS) shell material. The core–shell microcapsules were obtained by phase separation between the core component and the PDMS shell components after repartitioning of the common solvent THF between the PDMS/core material phase and the water phase. For the shell components, two commercially available functional PDMS polymers containing thiol and vinyl side groups were used. Photo-cross-linking in the presence of 2,2-dimethoxy-2-phenylacetophenone (DMPA) by thiol–ene radical addition was used to form a PDMS-thioether cross-linked shell. Variation of the PDMS component thiol to ene ratio resulted in different functionalities on the microcapsules surface and in the bulk, which was analyzed by attenuated total-reflection infrared spectroscopy (ATR-IR) and high-resolution magic-angle NMR-spectroscopy (HR-MAS NMR). Organically modified silica particles were mixed into the PDMS shell, resulting i...