The United States of America As Represented by the Department of Health

The United States of America As Represented by the Secretary of

Nenghua Guo

David D Roberts

Henry C Krutzsch

Joseph L Bryant

John K Inman

Philip J Browning

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.

Heparin and sulfatide binding peptides from the type-I repeats of human

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.

Heparin- and sulfatide binding peptides from the type I repeats of human

The present invention relates to peptides from the three type I repeats of human endothelial cell thrombospondin, which bind to sulfated glycoconjugates including heparin and sulfatide. Such peptides are useful in glycoconjugate binding pharmaceutical compositions and in a method for binding glycoconjugates in a subject.

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Gaithersburg, MD, United States of America

Nenghua Guo