Streptokinase mutants

A method for producing streptokinase mutants by expression of a gene encoding said mutant streptokinase which comprises the steps of transforming a host cell with an expression vector containing a streptokinase gene skc-2 fragment fused to the sequence tail Asp-Ile-Val-Asp-Gly-Gly-6xHis consisting essentially of the nucleotide sequence (Seq. ID. No. 12):

• AACAACAGCC AATTAGTTGT TAGCGTTGCT GGTACTGTTG AGGGGACGAA TCAAGACATT 60 AGTCTTAAAT TTTTTGAAAT TGACCTAACA TCACGACCTG CTCATGGAGG AAAGACAGAG 120 CAAGGCTTAA GTCCAAAATC AAAACCATTT GCTACTGATA GTGGCGCGAT GCCACATAAA 180 CTTGAAAAAG ACGACTTACT AAAGGCTATT CAAGAACAAT TGATCGCTAA CGTCCACAGT 240 AACGACGACT CATTTGAGGT CATTGATTTT GCAAGCGATC GAACCATTAC TGATCGAAAC 300 GGCAAGGTCT ACTTTGCTGA CAAAGATGGT TCGGTAACCT TGCCGACCCA ACCTGTCCAA 360 GAATTTTTGC TAAGCGGACA TGTGCGCGTT AGACCATATA AAGAAAAACC AATACAAAAT 420 CAAGCGAAAT CTGTTGATGT GGAATATACT GTACAGTTTA CTCCCTTAAA CCCTGATGAC 480 GATTTCAGAC CAGGTCTCAA AGATACTAAG CTATTGAAAA CACTAGCTAT CGGTGACACC 540 ATCACATCTC AAGAATTACT AGCTCAAGCA CAAAGCATTT TAAACAAAAC CCACCCAGGC 600 TATACGATTT ATGAACGTGA CTCCTCAATC GTCACTCATG ACAATGACAT TTTCCGTACG 660 ATTTTACCAA TGGATCAAGA GTTTACTTAC CATGTCAAAA ATCGGGAACA AGCTTATGAG 720 ATCAATAAAA AATCTGGTCT GAATGAAGAA ATAAACAACA CTGACCTGAT CTCTGAGAAA 780 TATTACGTCC TAAAAAAAGG GGAAAAGCCC TATGATCCCT TTGATCGCAG TCACTTGAAA 840 CTGTTCACCA TCAAATACGT TGATGTCAAC ACCAACGAAT TGCTAAAAAG CGAGCAGCTC 900 TTAACAGCTA GCGAACGTAA CTTAGACTTC AGAGATTTAT ACGATCCTCG TGATAAGGCT 960 AAACTACTCT ACAACAATCT CGATGCTTTT GGTATTATGG ACTATACCTT AACTGGAAAA 1020 GTAGAGGATA ATCACGATGA CACCAACCGT ATCATAACCG TTTATATGGG CAAGCGAGCC 1080 GAAGGAGAGA ATGCTAGCTA TCATTTAGCC TATGATAAAG ATGCTTATAC CGAAGAAGAA 1140 CGAGAAGTTT ACAGCTACCT GCGTTATACA GGGACACCTA TACCTGATAA CCCTAACGAC 1200 AAATAAGATA TCGTCGACGG GGGGCACCAC CACCACCACC ACTAA 1245

A method for producing streptokinase mutants by expression of a gene encoding said mutant streptokinase which comprises the steps of transforming a host cell with an expression vector containing a streptokinase gene skc-2 fragment consisting essentially of the nucleotide sequence (Seq. ID. No. 13):

• ATGATTGCTG GACCTGAGTG GCTGCTAGAC CGTCCATCTG TCAACAACAG CCAATTAGTT 60 GTTAGCGTTG CTGGTACTGT TGAGGGGACG AATCAAGACA TTAGTCTTAA ATTTTTTGAA 120 ATTGACCTAA CATCACGACC TGCTCATGGA GGAAAGACAG AGCAAGGCTT AAGTCCAAAA 180 TCAAAACCAT TTGCTACTGA TAGTGGCGCG ATGCCACATA AACTTGAAAA AGCTGACTTA 240 CTAAAGGCTA TTCAAGAACA ATTGATCGCT AACGTCCACA GTAACGACGA CTACTTTGAG 300 GTCATTGATT TTGCAAGCGA TGCAACCATT ACTGATCGAA ACGGCAAGGT CTACTTTGCT 360 GACAAAGATG GTTCGGTAAC CTTGCCGACG CAACCTGTCC AAGAATTTTT GCTAAGCGGA 420 CATGTGCGCG TTAGACCATA TAAAGAAAAA CCAATACAAA ATCAAGCGAA ATCTGTTGAT 480 GTGGAATATA CTGTACAGTT TACTCCCTTA AACCCTGATG ACGATTTCAG ACCAGGTCTC 540 AAAGATACTA AGCTATTGAA AACACTAGCT ATCGGTGACA CCATCACATC TCAAGAATTA 600 CTAGCTCAAG CACAAAGCAT TTTAAACAAA ACCCACCCAG GCTATACGAT TTATGAACGT 660 GACTCCTCAA TCGTCACTCA TGACAATGAC ATTTTCCGTA CGATTTTACC AATGGATCAA 720 GAGTTTACTT ACCATGTCAA AAATCGGGAA CAAGCTTATG AGATCAATAA AAAATCTGGT 780 CTGAATGAAG AAATAAACAA CACTGACCTG ATCTCTGAGA AATATTACGT CCTTAAAAAA 840 GGGGAAAAGC CGTATGATCC CTTTGATCGC AGTCACTTGA AACTGTTCAC CATCAAATAC 900 GTTGATGTCA ACACCAACGA ATTGCTAAAA AGCGAGCAGC TCTTAACAGC TAGCGAACGT 960 AACTTAGACT TCAGAGATTT ATACGATCCT CGTGATAAGG CTAAACTACT CTACAACAAT 1020 CTCGATGCTT TTGGTATTAT GGACTATACC TTAACTGGAA AAGTAGAGGA TAATCACGAT 1080 GACACCAACC GTATCATAAC CGTTTATATG GGCAAGCGAT AA 1122
• wherein said streptokinase mutants have reduced antigenicity compared to a full length SKC-2 streptokinase.

A method for producing streptokinase mutants by expression of a gene encoding said mutant streptokinase which comprises the steps of transforming a host cell with an expression vector containing a streptokinase gene skc-2 fragment fused to the sequence tail Asp-Ile-Val-Asp-Gly-Gly-6xHis consisting essentially of the nucleotide sequence (Seq. ID. No. 14):

• ATGATTGCTG GACCTGAGTG GCTGCTAGAC CGTCCATCTG TCAACAACAG CCAATTAGTT 60 GTTAGCGTTG CTGGTACTGT TGAGGGGACG AATCAAGACA TTAGTCTTAA ATTTTTTGAA 120 ATTGACCTAA CATCACGACC TGCTCATGGA GGAAAGACAG AGCAAGGCTT AAGTCCAAAA 180 TCAAAACCAT TTGCTACTGA TAGTGGCGCG ATGCCACATA AACTTGAAAA AGCTGACTTA 240 CTAAAGGCTA TTCAAGAACA ATTGATCGCT AACGTCCACA GTAACGACGA CTACTTTGAG 300 GTCATTGATT TTGCAAGCGA TGCAACCATT ACTGATCGAA ACGGCAAGGT CTACTTTGCT 360 GACAAAGATG GTTCGGTAAC CTTGCCGACC CAACCTGTCC AAGAATTTTT GCTAAGCGGA 420 CATGTGCGCG TTAGACCATA TAAAGAAAAA CCAATACAAA ATCAAGCGAA ATCTGTTGAT 480 GTGGAATATA CTGTACAGTT TACTCCCTTA AACCCTGATG ACGATTTCAG ACCAGGTCTC 540 AAAGATACTA AGCTATTGAA AACACTAGCT ATCGGTGACA CCATCACATC TCAAGAATTA 600 CTAGCTCAAG CACAAAGCAT TTTAAACAAA ACCCACCCAG GCTATACGAT TTATGAACGT 660 GACTCCTCAA TCGTCACTCA TGACAATGAC ATTTTCCGTA CGATTTTACC AATGGATCAA 720 GAGTTTACTT ACCATGTCAA AAATCGGGAA CAAGCTTATG AGATCAATAA AAAATCTGGT 780 CTGAATGAAG AAATAAACAA CACTGACCTG ATCTCTGAGA AATATTACGT CCTTAAAAAA 840 GGGGAAAAGC CGTATGATCC CTTTGATCGC AGTCACTTGA AACTGTTCAC CATCAAATAC 900 GTTGATGTCA ACACCAACGA ATTGCTAAAA AGCGAGCAGC TCTTAACAGC TAGCGAACGT 960 AACTTAGACT TCAGAGATTT ATACGATCCT CGTGATAAGG CTAAACTACT CTACAACAAT 1020 CTCGATGCTT TTGGTATTAT GGACTATACC TTAACTGGAA AAGTAGAGGA TAATCACGAT 1080 GACACCAACC GTATCATAAC CGTTTATATG GGCAAGCGAG ATATCGTCGA CGGGGGGCAC 1140 CACCACCACC ACCACTAA 1158