| 摘要 |
It has been found that agents which inhibit the interaction between the band 3 protein and its ligand (hereafter sometimes referred to as "interaction inhibitors" or "inhibitors"), CD36/thrombospondin, can also be used to enhance thrombolysis. The inhibitors can be peptides which contain sequences present in exofacial loops of the band 3 protein, or can be non-natural, D-isomer forms of the same sequences, or can be peptides, peptidomimetics, or non-peptidic molecules which interfere with band 3 protein-ligand interactions. One preferred group of such inhibitors comprises peptides characterized by the sequence motifZ2Z3Z2UX-UUUX- (SEQ ID NO:44),wherein Z2 represents a hydrophobic residue, U represents unobstructive residues, Z3 is either Z2 or an unobstructive residue and X- represents negatively charged residues. Another preferred group of such inhibitors comprises peptides characterized by the sequence motifZ1UKUUUX+ (SEQ ID NO:45),wherein Z1 is selected from the group consisting of tyrosine, phenylalanine and alanine; K is a lysine residue; U represents unobstructive residues; and X+ is a positively charged residue. The reverse sequences of these peptides are also active. The inhibitors of the subject method can be administered alone or in combination with one or more additional therapeutic agents. Administration can be oral, intravenous or by other means, in amounts between about 0.1 mg/kg to about 20 mg/kg.
|
