Faculty of Pharmacy, Lj. (FFALJ)
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Aktivnost analogov peptida RGD merjena z in vitro testom inhibicije gregacije trombocitov = Activity of RGD peptide analogues determined with in vitro test of platelet aggregation inhibition : diplomska nalogaZore, PetraBolezni srca in zilja so v razvitem svetu med najpogostejsimi boleznimi danasnjega èasa. Eden od vzrokov, ki lahko povzroèi srèno zilne bolezni, kot so arterijska in venska tromboza, pljuèna ... embolija, mozganska kap in srèni infarkt, je prekomerno nastajanje trombocitnih strdkov. Trombocitni strdek nastane zaradi agregacije trombocitov. Agregacijo trombocitov povzroèa vezava tripeptidnega zaporedja Arg-Gly-Asp (RGD) fibrinogena na glikoproteinski fibrinogenski receptor (GPIIbžIIIa). Antagonisti fibrinogenskega receptorja paz vezavo na ta receptor onemogoèijo vezavo fibrinogena in tako prepreèijo nastanek trombocitnega strdka. Razvoj antagonistov fibrinogenskega receptorja temelji na sintezi nepeptidnih Arg-Gly-Asp (RGD) analogov (peptidomimetikov) zustrezno biolosko uporabnostjo in selektivnostjo delovanja. S fotometrièno metodo merjenja agregacije trombocitov smo preizkusili 19 peptidomimetikov, potencialnih antagonistov fibrinogenskega receptorja. Agregacijo trombocitov smo izzvali z adenozin difosfatom (ADP) in kolagenom. Kot kontrolo smo uporabili antagoniste z znanim delovanjemČ Arg-Gly-Asp-Ser (RGDS), tirofiban in abciksimab. Rezultate smo podali kot koncentracije antagonistov, pri katerih se je odstotek agregacije in hitrost agregacije trombocitov zmanjsala na polovico (IC50). Dobljene vrednosti IC50 preizkusenih peptidomimetikov smo primerjali z dobljenimi vrednostmi za RGDS in iz tega sklepali na jakost delovanja potencialnih antagonistov fibrinogenskega receptorja. Ugotovili smo,da imajo peptidomimetiki SDJ-19-2.FR, SDJ-28, SDJ-27 in SDJ-36 precej veèjo jakost delovanja kot RGDSč SDJ-19, SJC-160, SDJ-19-1.FR, SDJ-12, SDJ-37 in DPS-254 so imeli podobno jakost delovanja. Peptidomimetiki STK-14, DPS-253 in SJC-41 so povzroèili rahlo inhibicijo agregacije, DPS-203, SMA-29b, SMA-67, DPS-204, SDJ-13 in SJC-161 pa 50 odstotne inhibicije agregacije oziroma hitrosti agregacije trombocitov niso povzroèili, ker smo jih testirali v prenizkih koncentracijah. Iz rezultatov, ki smo jih dobili za peptidomimetike SDJ-19-2.FR, SDJ-28, SDJ-27 in SDJ-36 lahko sklepamo, da gre za zelo dobre antagoniste agregacije trombocitov, iz katerih bi lahko z nadaljnjimi raziskavami razvili uèinkovito zdravilo za zdravljenje prekomernega strjevanja krvi.Type of material - undergraduate thesisPublication and manufacture - Ljubljana : [Zore P.], 2002Language - slovenianCOBISS.SI-ID - 1235057
Author
Zore, Petra
Other authors
Sollner Dolenc, Marija |
Stegnar, Mojca
Topics
hemostaza |
trombociti |
fibrinogenski receptor |
vpliv RGDS |
agregacija trombocitov |
metode
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Knjižnica dp 0000000542 Zore Petra Aktivnost IN: 0006741 Knjižnica dp 542 Zore Petra Aktivnost IN: 0006741 |
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Sollner Dolenc, Marija | 08519 |
Stegnar, Mojca | 05034 |
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