Patent ID: 6800286
Filing Date: 2004-10-05
Classification: A61K,C07K

Abstract:
A chimeric fibroblast growth factor-2 (FGF-2), comprising:a) a biologically active fibroblast growth factor-2 (FGF-2) protein having a first amino acid sequence that is encoded by a nucleic acid sequence that is at least about 90% identical to a nucleic acid sequence encoding a fibroblast growth factor-2 (FGF-2) protein represented by SEQ ID NO:5 or SEQ ID NO:6, wherein the FGF-2 protein has an FGF-2 biological activity selected from the group consisting of: promotion of cell proliferation, repression of terminal differentiation in a cell, promotion of angiogenesis, promotion of wound healing, promotion of osteogenesis, and promotion of nerve outgrowth; and, b) a penetratin peptide having a second amino acid sequence, wherein the penetratin peptide is selected from the group consisting of: i) a first peptide comprising an amino acid sequence selected from the group consisting of: 1) X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16; and, 2) X16-X15-X14-X13-X12-X11-X10-X9-X8-X7-X6-X5-X4-X3-X2-X1; wherein X1, X2, X3, X4, X5, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 each represent an &agr;-amino acid, between 6 and 10 of which are hydrophobic amino acids; and wherein X6 represents Trp; and, ii) a second peptide comprising amino acid residues 49-57 of HIV Tat protein (SEQ ID NO:17). wherein the biological activity of said penetratin peptide is to transport said chimeric fibroblast growth factor-2 (FGF-2) across a lipid bilayer of a cell independently of the presence of an FGF-2 receptor; wherein said second amino acid sequence is linked to said first amino acid sequence; andwherein said chimeric fibroblast growth factor-2 (FGF-2) is characterized by:i) said FGF-2 biological activity of (a) in the absence of heparan sulfate; and, ii) entry into a living cell in the absence of a receptor that binds to FGF-2.