Synthetic heparin-binding growth factor analogs
View Patent ↗The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.
1. A synthetic heparin-binding growth factor (HBGF) analog comprising a molecule having the formula (I):
wherein each X represents YRSRKYSSWYVALKR (SEQ ID NO:3), and
n is 1;
J 1 represents an amino acid;
J 2 represents a-diamino acid;
Y represents a linker that (i) is sufficiently hydrophobic to bind non-covalently to a polystyrene or polycaprolactone surface, (ii) comprises a chain of a minimum of about three and a maximum of about 17 residues, (iii) is not found in the natural ligand of the heparin-binding growth factor receptor (HBGFR), and (iv) is covalently bonded to J 2 and Z; and
Z represents a peptide that comprises a heparin binding domain, comprising RKRKLERAIR (SEQ ID NO:2) and
wherein the peptide analog has an avidity for heparin such that the synthetic heparin-binding growth factor analog binds heparin in 0.48M NaCl, but is eluted by 1M NaCl.
2. A synthetic heparin-binding growth factor analog according to claim 1 , consisting of a molecule of formula (I).
3. A synthetic heparin-binding growth factor analog according to claim 1 , wherein binding of the synthetic heparin-binding growth factor analog to the heparin-binding growth factor receptor initiates a signal by the heparin-binding growth factor receptor.
4. A synthetic heparin-binding growth factor analog according to claim 1 , wherein binding of the synthetic peptide to the heparin-binding growth factor receptor blocks signaling by the heparin-binding growth factor receptor.
5. A synthetic heparin-binding growth factor analog according to claim 1 , wherein J 1 and/or J 2 is an α-amino acid.
6. A synthetic heparin-binding growth factor analog according to claim 1 , wherein J 2 is lysine.
7. A synthetic heparin-binding growth factor (HBGF) analog comprising a molecule having the formula (I):
wherein each X represents YRSRKYSSWYVALKR (SEQ ID NO:3), and
n is 1;
J 1 represents lysine;
J 2 represents lysine;
Y represents a linker covalently bonded to J 2 and Z; and
Z represents a heparin binding sequence comprising RKRKLERAIR (SEQ ID NO:2).
8. The analog of claim 7 wherein Y is Hex-Hex-Hex (aminohexanoic acid tripeptide).