Positive modulator of bone morphogenic protein-2
View Patent ↗Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.
1. A compound of formula:
wherein:
X is a peptide chain that is AISMLYLDENEKVVL (SEQ ID NO: 7);
R 1 is independently a hydrogen (H—);
R 6 is independently a linker, wherein R 6 is a chain of 0 peptide bonds;
R 5 is a trifunctional alpha amino acid residue and, wherein X is covalently bonded to when R 6 is 0 peptide bonds;
R 4 is —NH2;
Y is a linker that is Ahx-Ahx-Ahx, wherein Ahx is 6-amino hexanoic acid; and
Z is RKRLDRIAR (SEQ ID NO: 5).
2. The compound of claim 1 wherein R 5 is an L- or D-diamine amino acid residue.
3. The compound of claim 2 wherein the L- or D-diamine amino acid residue is 2,3 diamino propionyl amino acid, 2,4 diamino butylic amino acid, lysine or ornithine.
4. The compound of claim 1 wherein X is covalently bonded to R 5 wherein the covalent bonds comprise an amide, disulfide, thioether, Schiff base, reduced Schiff base, imide, secondary amine, carbonyl, urea, hydrazone or oxime bond.
5. A compound having the following structure:
wherein Ahx is 6-amino hexanoic acid.
6. A bioactive implant having at least one coating comprising the compound of claim 1 .
7. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutical carrier.
8. The pharmaceutical composition of claim 7 further comprising a Bone Morphogenic Protein-2.