Ionotróp receptorok allosztérikus modulációja = Allosteric modulation of ionotropic receptors

A pentamer szerkezetű ionofór neurotranszmitter ?-aminovajsav, szerotonin és glicin receptorok (GABAAR, 5-HT3R, GlyR) szerkezetét és allosztérikus szabályozását vizsgáltuk meg. Az 5-HT3AR-ok pontmutációi és számítógépes modellezése antagonistáik kétféle kötődésmódját igazolták. Két fő neuroszteroidnak (allopregnanolon és THDOC) a GABAAR kötődésre és ionofór funkciója potencírozására kifejtett eltérő hatásai alapján a nanomoláris allopregnanolon az α6ßδ GABAAR-ok fiziológiás modulátora. Au allopregnanolon 17ß-származékát az első nanomólos affinitású, α6ßδ receptor- és sztereoszelektív neuroszteroid antagonistaként jellemeztük. Bifenil származékok gyulladásgátló és GABAAR-kötődési hatásainak szerkezeti kritériumait megkülönböztettük. 5-HT3 R antagonistákból kifejlesztettünk GlyR-okra és hiperekplexia mutánsukra szelektív potenciáló (nor)tropeineket. A heteroaromás tropein észterek heterogén GlyR-kötődésének nanomólos fázisát potenciáláshoz, a µmólost gátláshoz rendeltük. Az α1 GlyR pontmutációi és molekuladinamikai szimulációja alátámasztja az Arg-119 rotamerek és nortropeinek kötődésmódjai eltérő szerepét a GlyR-t gátló és potenciáló hatásokban. | The structures and allosteric modulation of pentameric ionotropic neurotransmitter receptors of ?-aminobutyric acid, serotonin and glycine (GABAAR, 5-HT3R, GlyR) were examined. Point mutations and computer modeling of 5-HT3ARs supported dual binding modes of antagonists. Based on different effects of two major neurosteroids, allopregnanolone and THDOC, on GABAAR binding and ionophore potentiation, nanomolar allopregnanolone is the physiologic modulator of α6ßδ GABAARs. Structural requirements of the anti-inflammatory and GABAAR-binding effects of biphenyl derivatives were distinguished. From 5-HT3 R antagonists (nor)tropeines were developed to selective potentiators of GlyRs and their hyperekplexia mutants. Nanomolar and micromolar phases of GlyR binding of heteroaromatic tropeine esters were attributed to potentiation and inhibition of GlyRs respectively. Point mutations of α1 GlyRs and molecular dynamic simulations supported the differential roles of Arg-119 rotamers and dual binding modes of nortropeines to block versus potentiate GlyRs

Nanostructures based on graphene and functionalized carbon nanotubes | Grafén és szén nanocső alapú nanoszerkezetek előállítása és jellemzése

In this thesis I have explored the preparation of graphene nanostructures, having crystallographically well defined edges and the scanning probe measurements of graphene and functionalized carbon nanotubes. The results of my research can be summarized in three main parts. I have developed a sample preparation technique, based on a carbon nanotube – few layer graphite composite that provides a simple and effective solution to sample stability issues encountered when measuring functionalized carbon nanotubes with STM. Such a composite has enabled for the first time to measure functionalized carbon nanotubes in atomic resolution, as well as to acquire energy resolved STM images of the tubes. Functionalized and pristine regions of the nanotube surface were made visible and the positions of the functional groups could be correlated with crystal lattice directions. The ease of the sample preparation allows the use of my method to study the properties of other types of functionalized carbon nanotubes. This adds STM to the toolbox of functionalized carbon nanotube characterization techniques, complementing optical spectroscopic methods. I have investigated the source of anomalous thickness measurements of graphene and few layer graphite, obtained by tapping mode AFM. The physical origin of these artefacts was elucidated by measurements and theoretical modeling of the AFM tip oscillation and tip – sample interaction. Numerical calculations and experiments have been used to show the correct experimental parameters needed to image the true thickness of graphene layers on a supporting substrate. The conclusions are general enough so that they can be applied to the measurements of other nanosized objects by AFM. I have demonstrated the existence of a chemical etching procedure that discriminates between the armchair and zigzag type edge termination of graphene layers. Coupled with AFM patterning, I have used this chemical process to pattern graphene sheets into nanostructures having zigzag edges. Raman measurements show that the edge roughness of these nanostructures is low enough that inelastic light scattering processes specific to the zigzag edge could be measured. This is the first study which shows that zigzag edged graphene nanostructures can be prepared in the laboratory in a controlled manner, which have a low enough edge disorder to enable the experimental observation of zigzag edge specific physical processes

Substrate-induced strain in carbon nanodisks

Abstract Graphitic nanodisks of typically 20 – 50 nm in thickness, produced by the so-called Kvaerner Carbon Black and Hydrogen Process were dispersed on gold substrate and investigated by atomic force microscopy (AFM), field emission scanning electron microscopy (FE-SEM), and confocal Raman spectroscopy. The roughness of the gold surface was drastically changed by annealing at 400 °C. AFM measurements show that this change in the surface roughness induces changes also in the topography of the nanodisks, as they closely follow the corrugation of the gold substrate. This leads to strained nanodisks, which is confirmed also by confocal Raman microscopy. We found that the FE-SEM contrast obtained from the disks depends on the working distance used during the image acquisition by In-lens detection, a phenomenon which we explain by the decrease in the amount of electrons reaching the detector due to diffraction. This process may affect the image contrast in the case of other layered materials, like hexagonal boron nitride, and other planar hybrid nanostructures, too