Fémionok és fémkomplexek kölcsönhatása makromolekuláris bioligandumokkal. = Interactions of metal ions with macromolecular bioligands.

I.Meghataroztuk a VO(IVes V) kolcsonhatasat jellemző kotesi allandokat a szerum transzferrinhez es albuminhoz es megallapitottuk, hogy a kulonboző antidiabetikus komplexek verben valo szallitasaban a transzferrin az elsődleges transzporter. Megallapitasainkat human szerum mintakon vegzett ex vivo HPLC-ICP-MS meresekkel kiserletileg is igazoltuk. Biszpiridin-, es biszdipeptid-szarmazekok kozott sikerult az Alzheimer korban alkalmazhato potencialis femkelator tipusu gyogyszermolekulakat talalni, melyek kepesek voltak a ?-amiloid oligomerizaciojat gatolni. Vizsgaltuk Al(III) komplexek hatasat az alkalikus foszfataz enzimre. Vizsgalataink arra utalnak, hogy a hordozo ligandumok kepesek kiszoritani az aktiv centrum femionjait, mig az Al(III) kepes helyettesiteni az egyik femiont. II.Szerkezeti es funkcionalis modellezes celjabol vizsgaltuk a Cu,ZnSOD, NiSOD es endostatin N-terminalis reszletet, Zn-transzporter feherjek femkotő szekvenciajat,HRG feherje His-gazdag regiojat es az MMP13 enzim aktiv centrumat modellező, illetve prolint es/vagy lizint tartalmazo peptidek femkomplexeit. A modellkomplexek kozul nehanyat szilard hordozon rogzitettunk. Nukleaz hatasu modelljeink hatekonyaknak bizonyultak modell-szubsztratok, DNS es RNS hasitasa soran. A specifikus mesterseges metalloenzimek vizsgalatanak első lepesekent molekulafelismeresi folyamatok es a lehetseges nukleaz domen melyebb megismeresere torekedtunk. Fuzios feherjek kolcsonhatasat vizsgaltuk femionokkal es DNS-sel. | I.Binding constants of VO(IV and V) to the serum proteins transferrin and albumin were determined and found that in transport of the different antidiabetic complexes in the blood transferrin is the primary transporter. This finding was confirmed by ex vivo HPLC-ICP-MS measurements made in real human samples. Chelators of bispyridyl and bis-dipeptide derivatives were synthetised against AD, which were able to inhibit oligomerization of ?-amyloids. The effect of various Al(III) complexes were studied on alkalaine phosphatase. It was assumed that the carrier ligands were able to displace the metal ions from the active center of the enzyme, while the metal ion was able to displace one of the metal ions in the active center. II.For structural and functional modelling we studied metal complexes of N-terminal fragments of a Cu,Zn-SOD, Ni-SOD and human endostatin, of the metal binding site of Zn-transporter, of the His-rich region of HRG, the acive centre of MMP13 proteins, as well as of proline and/or lysine containing peptides. Some model complexes were immobilized on a solid carrier. The models with nuclease activity proved to be efficient in cleavage of model-substrates, DNA and RNA. As a first step in the studies of specific artificial metalloenzymes we intended to deeply understand the molecular recognition processes and the properties of the possible nuclease domain. Fusion proteins have been expressed and their interaction with metal ions and DNA was studied.