Oldalláncban funkciós csoportot tartalmazó peptidek protonálódási és komplexképződési folyamatai. Makro- és mikroállandók meghatározása = Protonation and complex formation processes of peptides containing functional groups in their side chains. The determination of macroscopic and microscopic equilibria

Új módszert találtunk molekulák átfedő protonálódási folyamatainak követésére. Ezen módszer és 2D NMR technikák segítségével meghatároztuk számos, több hisztidint, lizint és karboxilcsoportot tartalmazó peptid protonálódási mikroállandóit. Összehasonlítottuk az emberben és csirkében található prion proteint. A betegségek kialakulása szempontjából a Cu(II) és Zn(II) mellett a Pd(II), Nil(II), Cd(II), Co(II), Mn(II) is fontos. Minden esetben sikerült igazolni az "octarepeat monomer" többi hisztidinhez (His96, 111 és 187) képesti gyengébb koordinációs képességét. A több (max. 4) hisztidint tartalmazó ligandumok esetén a koordinációs mikrofolyamatokat is felderítettük CD spektroszkópiával. A ?-amiloid modellek Cu(II)-, Zn(II)- és vegyes komplexeinek vizsgálata azt mutatta, hogy a réz(II)ion főleg a peptid N-ternimális végén kötődik. Zn(II) komplexinek stabilitása kisebb, ugyanakkor a Zn(II) a ligandum His13-14 részét preferálja. Két, két hisztidint és egy prolint tartalmazó hexapeptidet állítottam elő és vizsgáltam Cu(II)- és Pd(II)-ionnal. Ezen peptidek a természetes peptidekben is jelen lévő "turn" konformációt modellezik, és a biokémiai kutatások alapján a molekuláris felismerésben van szerepük. Több hisztidint tartalmazó peptideket (SOD és A?-modellek) vizsgáltunk Zn(II), Ni(II) és Cd(II)-ionnal. Cd(II) esetében a komplexek stabilitása még kisebb Zn(II)-vel, a Ni(II) viszont viszonylag stabil és változatosabb szerkezetű komplexeket képez. | New method was developped to determine overlapping deprotonation processes of molecules. Using this method together with further 2D-NMR techniques, microscopic deprotonation constants of several multihistidine, -lysine and -carboxyle peptides were determined. Metal complexes of the human and chicken prion protein were studied. In the formation of prion diseases, the coordination to Pd(II), Ni(II), Cd(II), Co(II), Mn(II) is also important in addition to Cu(II) and Zn(II) complexes. For all measured metals, the coordination strength of the "octarepeat monomer" region is weaker than that of the other histidines (96, 111, 187). For ligands containing more (max. 4) histidines the microscopic cordination processes were also determined using CD spectroscopy. The investigation of ?-amyloid segments with Cu(II) and Zn(II) shows that copper(II) coordinates mainly to the N-terminus of A?. The stabilities of Zn(II) complexes are much lower, coordination occurs at the His13-14 positions. Two systematically engineered, two-histidine and one-prolin containing hexapeptides were synthesized and investigated with Cu(II) and Pd(II). These peptides model the "turn" conformation of large biomolecules responsible for the molecular recognition. Multihistidine SOD and A? models were studied with Zn(II), Ni(II) and Cd(II). The stabilities of Cd(II) complexes are lower than those of Zn(II). Ni(II) forms more stable and more diverse complexes compared to the other two metals

Preliminary report on the paleopathological research of the skeletal material from the Szeged medieval castle excavation

This study introduces some diseases occurred among the medieval population of Szeged. Hitherto 641 individuals have undergone general anthropological investigations. The identification of abnormal bone conditions was mainly performed by gross examination, but in several cases further investigations were required.One of the most common pathological disorders was spinal osteoarthrosis. There were some skeletal evidences of trauma identifiable; particularly fractures of the ribs and upper limbs. The incidence of developmental defects in our skeletal population is moderate. We observed some cases of widespread skeletal hyperostosis (DISH) as well as localized cranial hyperostosis (HFI) and also traces of osteoporotic processes. Porotic hyperostosis, a skeletal symptom of some nutritional deficiencies and also specific diseases, is a common phenomenon in our material.We could notice traces of non-specific infections like isolated periostitis or osteomyelitis and also that of slight bone alterations that can be indicative of early stage tuberculosis. However, the typical angular kyphosis found in one case proves that TB was present in medieval Szeged. Three skeletons showed bone lesions caused possibly by acquired syphilis. In two cases the radiocarbon and archaeological dating suggested precolumbian origin. These treponemal cases complete the list of evidences of pre-Columbian treponematosis in the Old World

An Autocatalytic Step in the Reaction Cycle of Hydrogenase from Thiocapsa roseopersicina Can Explain the Special Characteristics of the Enzyme Reaction

AbstractA moving front has been observed as a special pattern during the hydrogenase-catalyzed reaction of hydrogen uptake with benzyl viologen as electron acceptor in a thin-layer reaction chamber. Such fronts start spontaneously and at random times at different points of the reaction chamber; blue spheres are seen expanding at constant speed and amplitude. The number of observable starting points depends on the hydrogenase concentration. Fronts can be initiated by injecting either a small amount of completed reaction mixture or activated hydrogenase, but not by injecting a low concentration of reduced benzyl viologen. These characteristics are consistent with an autocatalytic reaction step in the enzyme reaction. The special characteristics of the hydrogen-uptake reaction in the bulk reaction (a long lag phase, and the enzyme concentration dependence of the lag phase) support the autocatalytic nature. We conclude that there is at least one autocatalytic reaction step in the hydrogenase-catalyzed reaction. The two possible autocatalytic schemes for hydrogenase are prion-type autocatalysis, in which two enzyme forms interact, and product-activation autocatalysis, where a reduced electron acceptor and an inactive enzyme form interact. The experimental results strongly support the occurrence of prion-type autocatalysis

Az imidazolgyűrű biológiai szerepének modellezése bisz(imidazolil) és hisztidin-analóg származékok átmenetifém komplexeinek vizsgálatával = Modelling of the biological role of imidazole residues in the metal complexes of bis(imidazolyl) compounds and histidine analogues

A vizsgálataink célja a Cu,Zn-szuperoxid-diszmutáz (SOD) enzim Cu(II)- és Zn(II)-kötőhelyének tanulmányozása volt. A vizsgálatok három fő területen folytak. a) A bisz(imidazolil)csoportot tartalmazó aminosav- és peptidszármazékok átmenetifém komplexeinek vizsgálata azt mutatja, hogy a koordinálódó oldalláncot nem tartalmazó dipeptidszármazékok, illetve a hisztidint tartalmazó aminosavszármazék Cu(II) komplexe lehet potenciális modellje a SOD enzimnek. A bisz(imidazolil)csoport erős fémmegkötő tulajdonsága révén jelentősen megváltoztatja a peptidek koordinációs sajátságait. Ez a csoport képes horgonycsoportként elősegíteni az amidnitrogének deprotonálódását és koordinálódását Cu(II), Ni(II), és néhány esetben a Zn(II), VO(IV)-ionok esetén is. A potenciális donorcsoportok nagy száma változatos szerkezetű ligandum-, illetve imidazolhidas többmagvú izomer komplexek képződését eredményezi. b) A két- vagy több hisztidint és/vagy aszparaginsavat tartalmazó oligopeptidek a SOD enzim aktív centruma kötőhelyének megfelelő aminosavszekvenciát tartalmazzák. A hisztidinek kötödése ugyanahhoz a fémionhoz nagymértékben megnöveli az ML komplexek stabilitását. Az ML komplexek stabilitása a HisXaaHisYaaHis szekvenciát tartalmazó peptidek esetén a legnagyobb. c) A hisztidinnel analóg aminosav- és peptidszármazékok esetén az aromás gyűrű hatása az aminosav-, illetve peptidszerű koordinációra az imidazol > piridin ~ triazolil > tiazolil ~ tienil sorrendben csökken. | The main aim of our research was the study of Cu(II) and Zn(II) binding site of Cu,Zn superoxide dismutase. Our studies were performed in three fields: a) The studies on transition metal complexes of amino acid and peptide derivatives of bis(imidazolyl) group revealed that the copper(II) complex of dipeptides containing non-coordinating side chains and the histidine containing amino acid derivatives potentially mimic the SOD enzyme. Due to the strong metal binding ability of bis(imidazolyl) group it influences significantly the coordination behaviour of peptides. This group as an anchor is able to promote the deprotonation and coordination of amide nitrogens in the Cu(II), Ni(II) and in some cases in Zn(II) and VO(IV) complexes. The presence of numerous donor groups in the ligands, however, results in the formation of various isomeric dinuclear complexes with ligand- or imidazole bridges. b) The studied ligands containing two or more histidines and/or aspartic acids correspond to the amino acid sequence of active site of SOD enzyme. The binding of histidine side chains to the same metal ions significantly enhances the stability of ML complexes. The highest stability of ML complexes was detected in the case of peptide containing HisXaaHisYaaHis sequence. c) For histidine analogue amino acids and peptides the heteroaromatic rings influences the amino acid or peptide like coordination mode in the order imidazole > pyridine ~ triazolyl > thiazolyl ~thienyl rings

Copper(II) Complexes of Amino Acids and Peptides Containing Chelating bis(imidazolyl) Residues

Copper(II) complexes of amino acids and peptides containing the chelating bis(imidazolyl) residues have been reviewed. The results reveal that bis(imidazolyl) analogues of these biomolecules are very effective ligands for metal binding. The nitrogen donor atoms of the chelating agent are the major metal binding sites under acidic conditions. In the presence of terminal amino group the multidentate character of the ligands results in the formation of various polynuclear complexes including the ligand and the imidazole bridged dimeric species. The most intriguing feature of the coordination chemistry of these ligands is that the deprotonation of the coordinated imidazole-N(1)H groups results in the appearance of a new chelating site in the molecules. It leads to the formation of stable trinuclear complexes via negatively charged imidazolato bridges

Virginiamycin, valamint virginiamycin és furazolidon egymás melletti meghatározása állat-tápszerekben

Es wurde auf Grund von 380 vergleichenden Untersuchungen bestätigt, dass zur mikrobiologischen Wertmessung des Virginiamycins die Testorganismen Micrococcus flavus ATCC 1024 und Sarcina lutea ATCC 9341 die günstigsten sind. Dichlormethan und eine 20 cm3 Äthanol enthaltende PbS-Lösung vom pH 6 waren die geeignetsten Lösungsmittel. Es wurde eine Methode entwickelt, die die Bestimmung des Virginiamycins und Furazolidons in Gegenwart von beiden Verbindungen im Untersuchungs-material nach dem Aufschluss mittels Dichlormethan ermöglicht. It was found on the basis of 380 comparative investigations that the test organisms Micrococcus flavus ATCC 1024 and Sarcina lutea ATCC 9341 represent for the microbiological evaluation of virginiamycin the most suitable organisms. As a solvent dichloromethane and a PbS solution containing 20 cm3 ethanol and adjusted to pH 6 proved the most appropriate. A method was developed for the determination of virginiamycin and furazolidone in the presence of each other in the investigated sample after its treatment with dichloromethane