Isolated polypeptides and compositions from the venom of P. transvaalicus and methods of use
AssigneeThe Regents of the University of California
InventorsBruce D. Hammock, Bora Inceoglu
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Abstract
The invention provides isolated polypeptides from the venom of the scorpion P. transvaalicus. The invention also provides novel scorpion antivenom compositions derived from such polypeptides, as well as methods for isolating the polypeptides and preparing scorpion antivenom compositions. The isolated polypeptides can be used to produce pharmaceutical compositions useful for treating diseases and conditions associated with ion channel function or kinin activity.
Claims40
An isolated birtoxin family polypeptide comprising at least 20 amino acids of the sequence of any one of SEQ ID NOS:1-5.
An isolated polypeptide comprising at least 6 amino acids of the sequence of any one of SEQ ID NOS:27-30.
An isolated polypeptide, wherein said polypeptide comprises the amino acid sequence of any one of SEQ ID NOS:1-5 and SEQ ID NOS:27-30.
A scorpion birtoxin family polypeptide separated from its natural milieu.
An isolated bradykinin-like polypeptide comprising the sequence X1(X2)nX3X4X5X6PX7R, wherein X1 is at the N-terminus of the polypeptide and wherein X1 is any modified amino acid, (X2)n is contiguous sequence of any amino acids of length n, where n is from 0 to about 30, P is Pro, R is Arg, X4 is Ile, Leu or Val and X3, X5 X6 and X7 are any amino acids.
An isolated bradykinin-like polypeptide comprising the sequence X1X2X3X4X5PX6R, wherein X1 is at the N-terminus of the polypeptide and wherein X3 is Ile, Leu or Val, P is Pro, R is Arg, and X1,X2,X3, X4, X5 and X6 are any amino acids.
A scorpion bradykinin-like polypeptide separated from its natural milieu.
An isolated antibody which specifically binds a polypeptide comprising the sequence of any one of SEQ ID NOS:1-5 and SEQ ID NOS:27-30, or an antigenic epitope thereof.
An isolated polynucleotide which encodes a polypeptide comprising at least about 6 contiguous amino acids of the sequence of any one of SEQ ID NOS:1-5 and SEQ ID NOS:27-30.
A method of identifying a substance which modulates a ion channel binding activity of a birtoxin family polypeptide, comprising:
- a) contacting the substance with a sample containing a birtoxin family polypeptide and an ion channel;
- and
- b) assaying a ion channel binding activity of birtoxin family polypeptide in the presence of the substance, wherein an increase or a decrease in ion channel binding activity of birtoxin family polypeptide in comparison to ion channel binding activity of birtoxin family polypeptide in a suitable control is an indication that the substance modulates ion channel activity.
A method of modulating binding of a birtoxin family polypeptide to an ion channel, comprising:
- contacting a sample comprising a birtoxin family polypeptide and an ion channel with a specific modulator of birtoxin family polypeptide-ion channel.
A method comprising contacting ion channels of cells with a composition comprising a pharmaceutically acceptable carrier and a peptide having at least 20 amino acids of the sequence of any one of SEQ ID NOS:1-5.
A method of identifying a substance which modulates a receptor binding activity of a parakinin family polypeptide, comprising:
- a) contacting the substance with a sample containing a parakinin polypeptide and an kinin receptor;
- and
- b) assaying kinin receptor binding activity of the parakinin polypeptide in the presence of the substance, wherein an increase or a decrease in kinin receptor binding activity of parakinin polypeptide in comparison to kinin receptor binding activity of parakinin polypeptide in a suitable control is an indication that the substance modulates kinin receptor activity.
A method of modulating a kinin-associated disease or condition, comprising contacting a subject in need of treatment with a polypeptide comprising the comprising the sequence X1(X2)nX3X4X5X6PX7R, wherein X is at the N-terminus of the polypeptide and wherein X1 is any amino acid, (X2)n is contiguous sequence of any amino acids of length n, is from 0 to about 30, P is Pro, R is Arg, X4 is Ile Leu or Val and X3, X5 X6 and X7 are any amino acids, P is an aromatic amino acid of the D-conformation, whereby at least one symptom of the kinin-associated disease or condition is at least reduced.
A method comprising bringing an insect into contact with a composition comprising a peptide having at least 20 amino acids of the sequence of any one of SEQ ID NOS:1-5 and SEQ ID NOS:27-30.
A method comprising bringing a pest into contact with a composition comprising a peptide having at least 20 amino acids of the sequence of any one of SEQ ID NOS:1-5 and SEQ ID NOS:27-30.
Dependencies are inferred from the claim text.