Plasmin inhibitors from the australian brown snake Pseudonaja textilis textilis
AssigneesThe University of Queensland, National Institute of Biological Standards and Control
InventorsPantaleone Paul Masci, Martin Francis Lavin, Patrick Joseph Gaffney
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Abstract
The invention provides novel single stage competitive inhibitors of plasmin from the Australian brown snake Pseudonaja textilis textilis. The invention also features polynucleotides and polynucleotide homologues encoding these inhibitors. Pharmaceutical compositions containing the plasmin inhibitors of the invention are also disclosed as well as methods useful for treatment of blood loss.
Claims48
A substantially pure preparation of a plasmin inhibitor characterised in that it is a single stage competitive inhibitor of plasmin, wherein “substantially pure” means that at least 60% of the total material in the preparation is the plasmin inhibitor, and wherein the plasmin inhibitor comprises a polypeptide with at least 90% sequence identity to one selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, and the general formula:
- KDZPZŸCZLBBZBGXCZXXXBXFÃYXBZZZZCBZFBYGGCXBNANNFXTXEECE STCAA (I) (SEQ ID NO 67), wherein:
- X is any amino acid selected from the group consisting of Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val, α-aminobutyric acid, L-N-methylalanine, α-amino-α-methylbutyrate, L-N-methylarginine, aminocyclopropane-carboxylate, L-N-methylasparagine, aminoisobutyric acid, L-N-methylaspartic acid, aminonorbornyl-carboxylate, L-N-methylcysteine, cyclohexylalanine, L-N-methylglutamine, cyclopentylalanine, L-N-methylglutamic acid, L-N-methylisoleucine, L-N-methylhistidine, D-alanine, L-N-methylleucine, D-arginine, L-N-methyllysine, D-aspartic acid, L-N-methylmethionine, D-cysteine, L-N-methylnorleucine, D-glutamate, L-N-methylnorvaline, D-glutamic acid, L-N-methylornithine, D-histidine, L-N-methylphenylalanine, D-isoleucine, L-N-methylproline, D-leucine, L-N-medlylserine, D-lysine, L-N-methylthreonine, D-methionine, L-N-methyltryptophan, D-ornithine, L-N-methyltyrosine, D-phenylalanine, L-N-methylvaline, D-proline, L-N-methylethylglycine, D-serine, L-N-methyl-t-butylglycine, D-threonine, L-norleucine, D-tryptophan, L-norvaline, D-tyrosine, α-methyl-aminoisobutyrate, D-valine, α-methyl-γ-aminobutyrate, D-α-methylalanine, α-methylcyclohexylalanine, D-α-methylarginine, α-methylcylcopentylalanine, D-α-methylasparagine, α-methyl-α-napthylalanine, D-α-methylaspartate, α-methylpenicillamine, D-α-methylcysteine, N-(4-aminobutyl)glycine, D-α-methylglutamine, N-(2-aminoethyl)glycine, D-α-methylhistidine, N-(3-aminopropyl)glycine, D-α-methylisoleucine, N-amino-α-methylbutyrate, D-α-methylleucine, α-napthylalanine, D-α-methyllysine, N-benzylglycine, D-α-methylmethionine, N-(2-carbamylediyl)glycine, D-α-methylornithiine, N-(carbamylmethyl)glycine, D-α-methylphenylalanine, N-(2-carboxyethyl)glycine, D-α-methylproline, N-(carboxymethyl)glycine, D-α-methylserine, N-cyclobutylglycine, D-α-methylthreonine, N-cycloheptylglycine, D-α-methyltryptophan, N-cyclohexylglycine, D-α-methyltyrosine, N-cyclodecylglycine, L-α-methylleucine, L-α-methyllysine, L-α-methylmethionine, L-α-methylnorleucine, L-α-methylnorvatine, L-α-methylornithine, L-α-methylphenylalanine, L-α-methylproline, L-α-methylserine, L-α-methylthreonine, L-α-methyltryptophan, L-α-methyltyrosine, L-α-methylvaline, L-N-methylhomophenylalanine, N-(N-(2,2-diphenylethyl carbamylmethyl)glycine, N-(N-(3,3-diphenylpropyl carbamylmethyl)glycine, and 1-carboxy-1-(2,2-diphenyl-ethyl amino)cyclopropane;
- Ÿ is a hydrophobic amino acid;
- Ã is an aromatic amino acid;
- Z is K, R, H, D, E, Q or N;
- and
- B is a neutral amino acid, or P, A, G, S, T, V or L.
Dependencies are inferred from the claim text.