.alpha.-1-antichymotrypsin analogues having chymase...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/15 (2006.01) A61K 38/57 (2006.01) C07K 14/81 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2186635

The invention provides analogues of .alpha.-1-antichymotrypsin having amino acid substitutions at positon 358. .alpha.-1-antichymotrypsin analogues having amino acid substitutions at positions 356-361 and analogues having amino acid substitutions at positions 356-361 wherein the amino acid at position 358 is substituted are also within the scope of the invention. These analogues exhibit chymase inhibitory activity. Also provided are novel .alpha.-1-antichymotrypsins having an N-terminal extension of methionine-alanine-serine or alanine-serine. Expression vectors for the production of .alpha.-1-antichymotrypsins are also provided. The present invention also provides host cells and cell cultures capable of expressing analogues of .alpha.-1-antichymotrypsins, as well as protein preparations from the host cells. Methods of producing and using the analogues of .alpha.-1-antichymotrypsins to inhibit chymase activity are also provided.

L'invention concerne des analogues de la .alpha.-1-antichymotrypsine présentant une substitution de l'acide aminé en position 358. Les analogues de la .alpha.-1-antichymotrypsine présentant des substitutions d'acides aminés aux positions 356-361 et les analogues présentant des substitutions d'acides aminés aux positions 356-361, dans lesquels l'acide aminé en position 358 est substitué, sont également concernés par l'invention. Ces analogues présentent une activité inhibitrice vis-à-vis de la chymase. L'invention concerne également de nouvelles .alpha.-1-antichymotrypsines ayant une extension N-terminale de méthionine-alanine-sérine ou d'alanine-sérine. On fournit également des vecteurs d'expression pour la production de .alpha.-1-antichymotrypsines. La présente invention concerne en outre des cellules hôtes et des cultures de cellules capables d'exprimer les analogues de la .alpha.-1-antichymotrypsine ainsi que des préparations de protéines réalisées à partir des cellules hôtes. Sont aussi décrites des méthodes pour produire et utiliser les analogues de la .alpha.-1-antichymotrypsine pour inhiber l'activité de la chymase.

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