Thrombin activatable plasminogen analogues
AssigneeBritish Bio-Technology Limited
InventorsKeith Martyn Dawson, Richard James Gilbert, Michael George Hunter
Life of this patent
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Abstract
A plasminogen analogue activatable by thrombin to have plasmin activity which contains the cleavage site sequence (SEQ ID NO: 23): ##STR1## where Xaa at position 1 represents P4; Xaa at position 2 represents P3; Xaa at position 5 represents P1'; and Xaa at position 6 represents P2' where P3 is a basic amino acid residue, P4 is a hydrophobic amino acid residue and each of P1' and P2' is independently a non-acidic amino acid residue, said site being cleavable by thrombin between Arg and P1'.
Claims22
In a plasminogen having a cleavage site, the cleavage of which is catalyzed by tPA or uPA, the improvement wherein said cleavage site is replaced with a thrombin cleavage site which contains the sequence (SEQ ID NO:23):
- ##STR8## where Xaa at position 1 represents P4;
- Xaa at position 2 represents P3;
- Xaa at position 5 represents P1';
- and Xaa at position 6 represents P2' and wherein P3 is a basic amino acid residue selected from lysine or arginine, P4 is a hydrophobic amino acid residue selected from valine, isoleucine or leucine, and each of P1' and P2' is independently a non-acidic amino acid residue selected from valine, isoleucine or leucine, said site being clearable by thrombin between Arg and P1'.
A method of modifying a compound having plasminogen activity and having a cleavage site, the cleavage of which is catalyzed by tPA or uPA which comprises replacing said cleavage site with a thrombin cleavage site which contains the sequence (SEQ ID NO:23):
- ##STR17## where Xaa at position 1 represents P4;
- Xaa at position 2 represents P3;
- Xaa at position 5 represents P1';
- and Xaa at position 6 represents P2' and where P3 is a basic amino acid residue selected from lysine or arginine, P4 is a hydrophobic amino acid residue selected from valine, isoleucine or leucine, and each of P1' and P2' is independently a non-acidic amino acid residue selected from valine, isoleucine or leucine, said site being cleavable by thrombin between Arg and P1'.
Dependencies are inferred from the claim text.