Heparin and sulfatide binding peptides from the type-I repeats o

Details Heparin and sulfatide binding peptides from the type-I repeats o Heparin and sulfatide binding peptides from the type-I repeats o

1998-03-11

2000-04-18

Colba, Bennett

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 12, 514 13, 514 14, 514 15, 514908, 530300, 530324, 530326, 530327, 435 4, 435 13, A61K 3800, C07K 700

Patent

active

06051549&

ABSTRACT:
This invention identifies a biologically active group of peptide sequences from Type I repeat units of the extracellular matrix protein, human thrombospondin-1, identical or homologous to the sequence, KRFKQDGGWSHWSPWSSC (SEQ ID NO.30). The biological activities residing with the full sequences, portions thereof, and variants of the full or partial sequences are disclosed. The invention describes how biological activity may be enhanced by covalently linking these peptides to suitable carriers, preferably a branched, water-soluble polymer of low (or absent) toxicity and immunogenicity, such as polysucrose (Ficoll.TM.). The invention describes (1) a method for preparing such conjugates, (2) the use of the defined peptides or their conjugates in blocking or modifying the action on cellular processes of heparin (e.g., proliferation, adhesion, motility, extravasation and neovascularization), sulfatides, related sulfated glycoconjugates, fibronectin, and basic fibroblast growth factor, involving malignant cell lines and normal endothelial cells. Use of the defined peptides, analogs or peptidomimetics and their conjugates for treatment of metastatic tumors, breast carcinomas, melanomas, Kaposi's sarcomas, hemangiomas, diabetic retinopathies, and various pathological conditions dependent upon neovascularization is also disclosed.

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