Please use this identifier to cite or link to this item: https://olympias.lib.uoi.gr/jspui/handle/123456789/8291
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dc.contributor.authorMitsios, J. V.en
dc.contributor.authorStamos, G.en
dc.contributor.authorRodis, F. I.en
dc.contributor.authorTsironis, L. D.en
dc.contributor.authorStanica, M. R.en
dc.contributor.authorSakarellos, C.en
dc.contributor.authorTsoukatos, D.en
dc.contributor.authorTsikaris, V.en
dc.contributor.authorTselepis, A. D.en
dc.date.accessioned2015-11-24T16:40:34Z-
dc.date.available2015-11-24T16:40:34Z-
dc.identifier.issn0953-7104-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/8291-
dc.rightsDefault Licence-
dc.subjectplatelet activation inhibitorsen
dc.subjectpeptidesen
dc.subjectintegrin inhibitorsen
dc.subjectalpha(iib)beta(3) receptoren
dc.subjectglycoprotein-iib-iiiaen
dc.subjectintegrin alpha(iib)beta(3)en
dc.subjectgamma-chainen
dc.subjectpeptideen
dc.subjectadhesionen
dc.subjectreceptoren
dc.subjectcomplexen
dc.subjectsiteen
dc.subjectaggregationen
dc.subjectproteinsen
dc.titleInvestigation of the role of adjacent amino acids to the 313-320 sequence of the alpha(IIb) subunit on platelet activation and fibrinogen binding to alpha(IIb)beta(3)en
heal.typejournalArticle-
heal.type.enJournal articleen
heal.type.elΆρθρο Περιοδικούel
heal.identifier.primaryDoi 10.1080/09537100500436713-
heal.identifier.secondary<Go to ISI>://000239976000001-
heal.identifier.secondaryhttp://informahealthcare.com/doi/abs/10.1080/09537100500436713-
heal.languageen-
heal.accesscampus-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείαςel
heal.publicationDate2006-
heal.abstractThe platelet integrin receptor alpha(IIb)beta(3) plays a critical role in thrombosis and haemostasis by mediating interactions between platelets and several ligands, primarily fibrinogen. We have previously shown that the synthetic peptide YMESRADRKLAEVGRVYLFL corresponding to residues 313-332 of alpha(IIb), is a potent inhibitor of platelet aggregation and fibrinogen binding to alpha(IIb)beta(3), interacting with fibrinogen rather than the receptor. Furthermore, we have demonstrated that the biological activities of the above peptide are due to the sequence YMESRADR, which corresponds to residues 313-320. By using new synthetic peptide analogues we investigated the structural characteristics responsible for the biological activity of YMESRADR as well the possible influence of the adjacent amino acids on the peptide's biological potency. According to our results, the synthetic octapeptide YMESRADR, is a potent inhibitor of platelet aggregation and P-selectin expression. Furthermore, YMESRADR inhibits fibrinogen binding but it does not significantly influence the binding of PAC-1 to ADP-activated platelets. The inhibitory potency of YMESRADR was gradually diminished by deleting the YMES sequence from the amino terminus and prolonging the carboxyl terminus of this peptide with the KLAE sequence. Extension of YMESRADR towards the amino terminus with the GAPL sequence (GAPLYMESRADR) does not modify the biological activity of YMESRADR. Furthermore, extension of GAPLYMESRADR at its carboxy terminus with the KLAE sequence (GAPLYMESRADRKLAE) significantly diminished its biological potency. Substitution of E 315 with D significantly enhances antiaggregatory potency and completely abolishes the inhibitory effect on P-selectin expression. Importantly, the D-315-containing peptides inhibit to a similar extent both fibrinogen and PAC-1 binding to activated alpha(IIb)beta(3) in contrast to the E-315-containing peptide which only inhibits fibrinogen binding. In conclusion, the present study suggests that the YMESRADR sequence 313-320 of alpha(IIb), is an important functional region of the insert connecting the beta(2) and beta(3) antiparallel beta-strands of the W5 blade of the alpha(IIb) subunit. Structural changes significantly modify the biological properties of this region.en
heal.journalNamePlateletsen
heal.journalTypepeer reviewed-
heal.fullTextAvailabilityTRUE-
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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