Hybrid proteins of human plasminogen and human t-PA, pharmaceuti

Details Hybrid proteins of human plasminogen and human t-PA, pharmaceuti Hybrid proteins of human plasminogen and human t-PA, pharmaceuti

1992-09-29

1994-04-12

Hill, Jr., Robert J.

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

424 9463, 435212, 435219, 435226, 435217, C12N 964, C12N 1500, C12N 968, A61K 37547

Patent

active

053023900

ABSTRACT:
A hybrid plasminogen activator which comprises the five kringle domains of plasminogen linked to the B-chain of t-PA or u-PA via an amino acid sequence comprising, respectively, the t-PA cleavage site between residues 275 and 276 and the cysteine residue 264 of t-PA or the u-PA cleavage site between residues 158 and 159 and the cysteine residue 148 of u-PA, or a derivative of a plasminogen activator comprising the serine protease domain of t-PA or u-PA, in which the catalytic site essential for plasminogen activator activity is blocked by a 2-aminobenzoyl group substituted in the 3- or 4-position with a halogen atom and optionally further substituted with one or more weakly electron-withdrawing or electon-donating groups, wherein the pseudo first order rate constant for hydrolysis of the derivative is in the range 6.0.times.10.sup.-5 to 4.0.times.10.sup.-4 sec.sup.-1 when measured in a buffer system consisting of 0.05M sodium phosphate, 0.1M sodium chloride, 0.01% v/v detergent comprising polyoxyethylenesorbitan monoleate having a molecular weight of approximately 1300, at pH 7.4 at 37.degree. C.

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