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dc.date.accessioned2018-06-11T11:02:52Z
dc.date.available2018-11-28T23:31:34Z
dc.date.created2017-07-20T18:24:53Z
dc.date.issued2017
dc.identifier.citationKara, Emrah Manna, Dipankar Løset, Geir Åge Schneider, E L Craik, C S Kanse, Sandip . Analysis of the substrate specificity of Factor VII activating protease (FSAP) and design of specific and sensitive peptide substrates. Thrombosis and Haemostasis. 2017
dc.identifier.urihttp://hdl.handle.net/10852/61832
dc.description.abstractFactor VII (FVII) activating protease (FSAP) is a circulating serine protease that is likely to be involved in a number of disease conditions such as stroke, atherosclerosis, liver fibrosis, thrombosis and cancer. To date, no systematic information is available about the substrate specificity of FSAP. Applying phage display and positional scanning substrate combinatorial library (PS-SCL) approaches we have characterised the specificity of FSAP towards small peptides. Results were evaluated in the context of known protein substrates as well as molecular modelling of the peptides in the active site of FSAP. The representative FSAP-cleaved sequence obtained from the phage display method was Val-Leu-Lys-Arg-Ser (P4-P1’). The sequence X-Lys/Arg-Nle-Lys/Arg (P4-P1) was derived from the PS-SCL method. These results show a predilection for cleavage at a cluster of basic amino acids on the nonprime side. Quenched fluorescent substrate (Ala-Lys-Nle-Arg-AMC) (amino methyl coumarin) and (Ala-Leu-Lys-Arg-AMC) had a higher selectivity for FSAP compared to other proteases from the hemostasis system. These substrates could be used to measure FSAP activity in a complex biological system such as plasma. In histonetreated plasma there was a specific activation of pro-FSAP as validated by the use of an FSAP inhibitory antibody, corn trypsin inhibitor to inhibit Factor XIIa and hirudin to inhibit thrombin, which may account for some of the haemostasis-related effects of histones. These results will aid the development of further selective FSAP activity probes as well as specific inhibitors that will help to increase the understanding of the functions of FSAP in vivo. This research has been published in Thrombosis and Haemostasis. © 2017 Schattaueren_US
dc.languageEN
dc.titleAnalysis of the substrate specificity of Factor VII activating protease (FSAP) and design of specific and sensitive peptide substratesen_US
dc.typeJournal articleen_US
dc.creator.authorKara, Emrah
dc.creator.authorManna, Dipankar
dc.creator.authorLøset, Geir Åge
dc.creator.authorSchneider, E L
dc.creator.authorCraik, C S
dc.creator.authorKanse, Sandip
cristin.unitcode185,51,12,14
cristin.unitnameVaskulær patofysiologi
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.qualitycode1
dc.identifier.cristin1482718
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Thrombosis and Haemostasis&rft.volume=&rft.spage=&rft.date=2017
dc.identifier.jtitleThrombosis and Haemostasis
dc.identifier.doi10.1160/TH17-02-0081
dc.identifier.urnURN:NBN:no-64437
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn0340-6245
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/61832/2/Kara%2Bet%2Bal%2BT%2526H.pdf
dc.type.versionAcceptedVersion
dc.relation.projectNFR/251239


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