Thrombin inhibitors based on the amino acid sequence of hirudin
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United States of America Patent
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May 9, 2000
Issued Date -
N/A
app pub date -
Mar 20, 1995
filing date -
Jun 15, 1990
priority date (Note) -
Expired
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Abstract
A thrombin inhibitor comprising a first bulky hydrophobic portion interacting with the catalytic site of thrombin responsible for proteolysis and a second portion at least maintaining the hydrophobic and acidic character of amino acids 55 to 60 of native hirudin at the C-terminal non-catalytic region of N-acetyl-hirudin45-65. Between the first and second portions is a divalent linker moiety having a chain length of at least 10 carbon atoms. Connecting the first bulky hydrophobic portion and the linker is a peptidomimetic bond. Preferably, the bulky hydrophobic portion comprises at least one amino acid of D-configuration. The compounds are useful in the treatment of thrombotic disorders.
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