Mutant of the erythrina caffra type inhibitor and the use of...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/29 (2006.01) C07K 14/81 (2006.01) C12N 9/48 (2006.01) C12N 9/64 (2006.01) C12N 9/72 (2006.01)

Patent

CA 2215531

A polypeptide which has the activity of an inhibitor DE -3 from Erythrina caffra and which reversibly and selectively binds serine proteases from a protein mixture is obtainable by culturing prokaryotic or eukaryotic host cells which have been transformed or transfected with a nucleic acid that codes for the said polypeptide in a manner that allows the host cells to express the said polypeptide under suitable nutrient conditions and isolating the said polypeptide, wherein the polypeptide has an amino acid sequence which is functionally analogous to SEQ ID NO:2, has a partial region that is more than 85 % homologous to the region of amino acids 39 - 139 of this sequence, has two disulfide bridges and begins N-terminally with SEQ ID NO:4 or with a SEQ ID NO:4 extended N-terminally by methionine and has a binding capacity for tissue plasminogen activators of 1.25 MU/ml and more and is particularly suitable for purifying plasminogen activators such as tissue plasminogen activators (t-PA and derivatives).

L'invention concerne un procédé d'obtention d'un polypeptide ayant l'activité d'un inhibiteur DE-3 de l'Erythrina caffra et fixant de façon réversible et sélective des sérine-protéases provenant d'un mélange protéinique, par culture de cellules hôtes procaryotes ou eucaryotes transformées ou transfectées avec un acide nucléique codant pour le polypeptide précité, permettant ainsi aux cellules hôtes d'exprimer ledit polypeptide dans des conditions nutritives appropriées, ledit procédé concernant également l'isolement de ce polypeptide et étant caractérisé en ce que le polypeptide possède une séquence aminoacide fonctionnellement analogue de SEQ ID NO:2 dans une région partielle à plus de 85 % homologue de la région des aminoacides 39-139 de cette séquence, possède deux ponts disulfure et commence, à un N terminal, par SEQ ID NO:4, ou par un SEQ ID NO:4 prolongé en N terminal d'une méthionine, et possède une capacité de fixation pour des activateurs tissulaires du plasminogène égale ou inférieure à 1,25 MU/ml. Ledit polypeptide est particulièrement approprié pour la purification d'activateurs du plasminogène, tels que des activateurs tissulaires du plasminogène (t-PA et dérivés).

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