Peptide inhibitors of fibronectin and related collagen-binding proteins
AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsDavid D. Roberts, Henry C. Krutzsch, John M. Sipes, Neng-hua Guo, Eric Negre
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Abstract
Peptides derived from the second type 1 repeat of human endothelial cell thrombospondin which bind to the gelatin-binding domain of fibronectin have been isolated and synthetically produced. The peptides can be used to bind to fibronectin or other related collagen-binding proteins to inhibit fibronectin-dependent cell adhesion to collagen matrices and to inhibit interactions with collagen of other proteins that share homologies with the gelatin-binding domain of fibronectin.
Claims12
A method for binding fibronectin comprising contacting fibronectin with an effective amount of a composition comprising a peptide having a specific binding affinity for the gelatin-binding domain of fibronectin, said peptide having from 3 to 18 amino acids in length and consisting of the sequence (A),
- Xa--Xb--His--Trp--Xc, (A)
- wherein Xa is H or an amino acid sequence of from 1 to 13 amino acids derived from the consecutively occurring thrombospondin amino acid residues 394-420, Xb is serine, alanins, tryptophan, or threonine and Xc is OH, NH.sub.2, or an amino acid sequence of from I to 13 amino acids derived from the consecutively occurring human thrombospondin amino acid residues 424-450, and at least one of Xa and Xb includes a tryptophan residue located within three amino acid residues from Trp in sequence (A).
A method for inhibiting enzymatic activity of collagenase in a patient in need of such treatment, which comprises administering to said patient an effective amount of at least one peptide contained in a pharmaceutically acceptable excipient or carrier, wherein said peptide is a peptide having a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8.
A peptide composition having a specific binding affinity for fibronectin, consisting essentially of a peptide selected from the group consisting of peptides having SEQ ID NO:1, SEQ ID NO:12 and SEQ ID NO:13.
Dependencies are inferred from the claim text.