Találati lista | Tudóstér

001-es BibID:	BIBFORM033201
Első szerző:	Mendelboum Raviv, Shlomit (biológus)
Cím:	4-thio-deoxyuridylate modified thrombin aptamer and its inhibitory effect on fibrin clot formation, platelet aggregation and thrombus growrth on subendothelial matrix / S. Mendelboum Raviv, A. Horváth, J. Aradi, Z. Bagoly, F. Fazakas, Z. Batta, L. Muszbek, J. Hársfalvi
Dátum:	2008
ISSN:	1538-7933
Megjegyzések:	Background:?The consensus thrombin aptamer C15-mer is a single-stranded DNA of 15 nucleotides [d(GGTTGGTGTGGTTGG)] that was identified by the selection of thrombin-binding molecules from a large combinatorial library of oligonucleotides. It is capable of inhibiting thrombin at nanomolar concentrations through binding to a specific region within thrombin exosite 1. As has been shown in our earlier studies, the 4-thio-deoxyuridylate (s4dU)-containing oligonucleotides have high affinity for a number of proteins, due to the reduced hydrophilic character of the modified oligonucleotide. Methods:?Three different analogs of the original thrombin-inhibiting sequence, in which some of the thymidylate residues were replaced by 4-thio-deoxyuridylates, were synthesized. The inhibitory effect of modified aptamers was tested on thrombin-catalyzed fibrin clot formation and fibrinopeptide A release from fibrinogen, thrombin-induced platelet aggregation/secretion, and the formation of thrombus on coverslips coated with human collagen type III, thrombin-treated fibrinogen or subendothelial matrix of human microvascular endothelial cells. Results:?As compared with the C15-mer, the analog with the sequence GG(s4dU)TGG(s4dU)G(s4dU)GGT(s4dU)GG (UC15-mer) showed a 2-fold increased inhibition of thrombin-catalyzed fibrin clot formation, fibrinopeptide A release, platelet aggregation and secretion in human plasma and thrombus formation on thrombin-treated fibrinogen surfaces under flow conditions. Concerning the inhibition of thrombin-induced fibrin formation from purified fibrinogen and activation of washed platelets, UC15-mer was 3-fold and twelve-fold more effective than C15-mer, respectively.Conclusion:?The replacement of four thymidylate residues in C15-mer by 4-thio-deoxyuridylate resulted in a new thrombin aptamer with increased anticoagulant and antithrombotic properties.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban 4-thio-deoxyuridylate aptamer platelets thrombin thrombin exosite thrombus
Megjelenés:	Journal Of Thrombosis And Haemostasis. - 6 : 10 (2008), p. 1764-1771. -
További szerzők:	Horváth András (1976-) (vegyész) Aradi János (1942-) (biokémikus, vegyész) Bagoly Zsuzsa (1978-) (orvos) Fazakas Ferenc (1969-) (molekuláris biológus) Batta Zoltán Muszbek László (1942-) (haematológus, kutató orvos) Hársfalvi Jolán (1949-) (klinikai biokémikus)
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: