C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 14/435 (2006.01) A61K 38/17 (2006.01) A61P 7/02 (2006.01) C07K 1/00 (2006.01) C07K 19/00 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2471373
The invention relates to modified tridegins, polypeptides derived from SEQ ID No. 1, in which the modification is replacement of a cysteine residue and/or one of the following amino acids - Lys2, Lys7, His10, Gly12, Leu24, Tyr31, Phe34, Arg39, Ile45, Met48, Asp50, Pro55, Phe58, Asn60, Pro65, Arg66, by another amino acid and/or N- or C-terminal deletion, whereby the remaining polypeptide comprises at least the amino acid sequence DDIYQRXVXFPXLPL (SEQ ID NO.89) and/or a covalent bonding to polyethylene glycol. Said polypeptides are novel inhibitors of transglutaminases, in particular of Factor XIIIa, of the terminal enzymes in the blood coagulation cascade. The invention further relates to methods for production of said inhibitors and the use thereof as transglutaminase inhibitors.
L'invention concerne des polypeptides modifiés, des trigédines, dérivés de SEQ ID NO 1. La modification consiste en ce qu'au moins un reste cystéine et/ou un des acides aminés suivants : Lys2, Lys7, His10, Gly12, Leu24, Tyr31, Phe34, Arg39, Ile45, Met48, Asp50, Pro55, Phe58, Asn60, Pro65, Arg66, est(sont) substitué(s) par un autre acide aminé, et/ou le radical N ou C est supprimé. Le polypeptide restant contient au moins la séquence d'acide aminé DDIYQRXVXFPXLPL (SEQ ID NO 89), et/ou il existe une combinaison covalente avec le polyéthylène-glycol. Les polypeptides selon l'invention constituent de nouveaux inhibiteurs de transglutaminases, notamment du facteur XIIIa, de l'enzyme terminale de la cascade de coagulation sanguine. L'invention concerne en outre des procédés permettant de produire ces inhibiteurs, ainsi que leur utilisation comme inhibiteurs de transglutaminase.
Giersiefen Helmut
Ohlmann Marion
Pamp Tanja
Stoeckel Johannes
Curacyte Ag
Goudreau Gage Dubuc
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