Biológiailag jelentős nem-kovalens kölcsönhatások tanulmányozása: fehérje-kötődés, nukleinsav-kötődés, önszerveződés = Investigations on non-covalent interactions of biological importance: protein binding, nucleic acid binding, self-assembly

2010 
Nem-kovalens kolcsonhatasok (feherjekotődes, aggregacio) kiserleti vizsgalatara UV-Vis, fluoreszcencia es kiroptikai spektroszkopiai modszereket alkalmaztak, a vizsgalati mintak tisztitasat kromatografias (HPLC, kapillaris elektroforezis) technikakkal vegeztek. A human verplazma minor feherje komponensenek (alfa-1 savas glikoprotein, AGP) reszletes vizsgalata kimutatta, hogy az AGP genetikai variansai elterő, a kotődesi erőssegtől fuggő modon csokkentik a myeloid leukemia gyogyszerenek (Imatinib, Glivec', Novartis) hatasossagat. Daganatos betegek klinikai vermintaibol kidolgoztak nagy tisztasagu AGP kinyereset es kapillaris elektroforezissel igazoltak, hogy az AGP cukorlancanak valtozatossaga (glycoform heterogeneity) kulonfele daganatos megbetegedesek erzekeny markere. Enantiomerek elvalasztasara egy ciklodextrin szarmazekot tartalmazo uj kiralis allofazist fejlesztettek ki. Megfigyeltek, hogy AGP kotődesben kiralis inverzio kovetkezhet be. A kiroptikai spektrumokban megjelenő exciton savpar intenzitasat nem-kovalens kolcsonhatasok esetere elmeleti alapon indokoltak. | UV-Vis, fluorescence and chiroptical spectroscopic methods have been applied for experimental studies of non-covalent interactions, the purification of the samples were done by chromatographic (HPLC, capillary electrophoresis) techniques. Detailed studies of the minor protein component of human blood plasma, alpha-1 acid glycoprotein (AGP) revealed that the decrease in the efficiency of the medication against chronic myelogenous leukaemia, Imatinib (Glivec', Novartis) brought about by the genetic variants of AGP was in correlation with their binding strength. Highly purified AGP samples were prepared from clinical blood samples of cancer patients and their capillary electrophoretic analysis proved the variability of sugar-chain of AGP (glycoform heterogeneity) to be a sensitive marker of several malignant diseases. New chiral stationary phase containing a cyclodextrin derivative has been developed for enantiomer separation. Chiral inversion has been demonstrated in AGP binding. The intensity of exciton couplets appearing in chiroptical spectra has been explained on theoretical grounds for non-covalent interactions.
    • Correction
    • Source
    • Cite
    • Save
    • Machine Reading By IdeaReader
    0
    References
    0
    Citations
    NaN
    KQI
    []