Inhibitors of glycosaminoglycans
The present invention provides peptide derivatives with a specific affinity for glycosaminoglycan molecules. These peptide derivatives include multimers as well as chemically modified peptides and may be prepared by a variety of methods. The peptides of the invention have numerous functions, including but not limited to use as inhibitors of glycosaminoglycan-mediated signaling events and targeting agents. Peptides of the invention may be directed against any glycosaminoglycan, including hyaluronic acid, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, heparin, keratan sulfate, keratosulfate, chitin, chitosan 1, and chitosan 2. The peptide derivatives of the invention also have therapeutic uses in the treatment and prevention of diseases involving inflammatory diseases, cancer, and cancer metastasis, autoimmune diseases, etc.
1. An artificial multimer of two to four peptides joined via a linker, wherein each of said peptides consists essentially of the amino acid sequence set forth in SEQ ID NO:1, and wherein said multimer binds hyaluronic acid with a binding affinity K a of at least 5×10 5 l/mol.
2. The artificial multimer of two to four peptides of claim 1 , wherein said multimer comprises two to four peptides having the same amino acid sequence.
3. The artificial multimer of two to four peptides of claim 1 , wherein said multimer comprises two to four peptides having different amino acid sequences.
4. The artificial multimer of two to four peptides of claim 1 , wherein said multimer is a dimer.
5. The artificial multimer of two to four peptides of claim 1 , wherein said multimer is a tetramer.
6. An artificial multimer of two to four peptides, wherein each of said peptides consists essentially of the amino acid sequence GAXWQFXALTVXGGGS, SEQ ID NO. 18 wherein X is any amino acid and wherein said multimer binds hyaluronic acid with a binding affinity K a of at least 5×10 5 l/mol.
7. A pharmaceutical composition comprising:
(a) an artificial multimer of claim 1 ; and
(b) a pharmaceutically acceptable carrier.
8. An artificial multimer of two to four peptides joined via a linker, wherein each of said peptides consists essentially of the amino acid sequence set forth in SEQ ID NO:2, and wherein said multimer binds hyaluronic acid with a binding affinity K a of at least 5×10 5 l/mol.
9. The artificial multimer of claim 6 , wherein the peptides consist essentially of the amino acid sequence GAHWQFNLATVRGGGS (SEQ ID NO:15).