EXOSITE-DIRECTED THROMBIN INHIBITORS
Disclosed are an amino acid sequence of the human blood clotting factor Va, peptides containing such sequence, and additional peptides of interest that significantly inhibit thrombin generation. Also disclosed are pharmaceutical compositions containing these peptides and related therapeutic methods for inhibiting thrombin generation and treating blood coagulation disorders.
1 - 111 . (canceled)
112 . A method for inhibiting thrombin generation in a human patient suffering from a blood coagulation disorder, the method comprising:
providing a pharmaceutical composition comprising a peptide including an amino acid sequence DYDY (SEQ ID NO. 10) and a carrier;
administering to the human patient, the pharmaceutical composition such that the amount of the peptide is in the range of from about 0.01 to 1000 mg/kg of body weight of the human patient, per day.
113 . The method of claim 112 wherein one of the Y amino acids of the amino acid sequence is sulfonated.
114 . The method of claim 113 wherein the amino acid sequence is DY(—SO 3 )DY.
115 . The method of claim 113 wherein the amino acid sequence is DYDY(—SO 3 ).
116 . The method of claim 112 wherein both the Y amino acids of the amino acid sequence are sulfonated.
117 . The method of claim 116 wherein the amino acid sequence is DY(—SO 3 )DY(—SO 3 ).
118 . The method of claim 112 wherein the amount of the peptide is in the range of from about 0.1 to 100 mg/kg of body weight, per day.
119 . The method of claim 118 wherein the amount of the peptide is in the range of from about 1 to 10 mg/kg of body weight, per day.
120 . A method for inhibiting thrombin generation in a patient suffering from a blood coagulation disorder, the method comprising:
administering to the patient an effective amount of a peptide analogue that mimics the peptide of the method of claim 112 .
121 . A method for inhibiting thrombin generation in a human patient suffering from a blood coagulation disorder, the method comprising:
providing a pharmaceutical composition comprising a peptide including an amino acid sequence DYDYQ (SEQ ID NO. 11) and a carrier;
administering to the human patient, the pharmaceutical composition such that the amount of the peptide is in the range of from about 0.01 to 1000 mg/kg of body weight of the human patient, per day.
122 . The method of claim 121 wherein one of the Y amino acids of the amino acid sequence is sulfonated.
123 . The method of claim 122 wherein the amino acid sequence is DY(—SO 3 )DYQ.
124 . The method of claim 122 wherein the amino acid sequence is DYDY(—SO 3 )Q.
125 . The method of claim 121 wherein both of the Y amino acids of the amino acid sequence are sulfonated.
126 . The method of claim 125 wherein the amino acid sequence is DY(—SO 3 )DY(—SO 3 )Q.
127 . The method of claim 121 wherein the effective amount of the peptide is in the range of from about 0.1 to 100 mg/kg of body weight, per day.
128 . The method of claim 127 wherein the effective amount of the peptide is in the range of from about 1 to 10 mg/kg of body weight, per day.
129 . A method for inhibiting thrombin generation in a patient suffering from a blood coagulation disorder, the method comprising:
administering to the patient an effective amount of a peptide that mimics the peptide of the method of claim 121 .