Single branch heparin-binding growth factor analogs

Inactive Publication Date: 2008-09-18
BIOSURFACE ENG TECH
View PDF68 Cites 19 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0057]In another aspect of the present invention, X of any of formulas I-VI comprises an amino acid sequence found in any of FGF-1, FGF-2, FGF-3, FGF-4, FGF-5, FGF-6, FGF-7, FGF-8, FGF-9, FGF-10, FGF-11, FGF-12, FGF-13, FGF-14, FGF-15, FGF-16, FGF-17, FGF-18, FGF-19, FGF-20, FGF-21, FGF-22, FGF-23, HBBM (heparin-binding brain mitogen), HB-GAF (heparin-binding growth associated factor), HB-EGF (heparin-binding EGF-like factor) HB-GAM (heparin-binding growth associated molecule, also known as pleiotrophin, PTN, HARP), TGF-α (transforming growth factor-α), TGF-βs (transforming growth factor-βs), VEGF (vascular endothelial growth factor), EGF (epidermal growth factor), IGF-1 (insulin-like growth factor-1), IGF-2 (insulin-like growth factor-2), PDGF (platelet derived growth factor), RANTES, SDF-1, secreted frizzled-related protein-1 (SFRP-1), small inducible cytokine A3 (SCYA3), inducible cytokine subfamily A member 20 (SCYA20), inducible cytokine subfamily B member 14 (SCYB14), inducible cytokine subfamily D member 1 (SCYD1), stromal cell-derived factor-1 (SDF-1), thrombospondins 1, 2, 3 and 4 (THBS1-4), platelet factor 4 (PF4), lens epithelium-der

Problems solved by technology

HBGFs useful in prevention or therapy of a wide range of diseases and disorders may be purified from natural sources or produced by recombinant DNA methods, however, such preparations are expensive and generally difficult to prepare.
However, none of the disclosed compositions further include two receptor-binding domains linked to a single residue through a terminal group and a side chain group of the single residue.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Single branch heparin-binding growth factor analogs
  • Single branch heparin-binding growth factor analogs
  • Single branch heparin-binding growth factor analogs

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0190]A compound of the present invention was synthesized by solid phase peptide chemistry with the general structure of formula I wherein X is a BMP-2 receptor binding amino acid sequence having the sequence AISMLYLDEKVVL(SEQ ID NO:105) wherein the sequence was grown in parallel from the R1 trifunctional amino acid of formula I when R2 is 0 atoms and R1 is lysine. The resulting synthetic growth modulator analog is of the following specific structure:

and is sometimes called B2A2-K-NS. In the foregoing structure, “Ahx” is 6-amino hexanoic acid, sometimes also called “6-Ahx” or “Hex”. The single letters are standard amino acid single letter abbreviations for the naturally coded amino acids.

example 2

[0191]A compound of the present invention was synthesized by solid phase peptide chemistry with the general structure of formula I wherein X is a BMP receptor binding amino acid sequence having the sequence LYFDESSNVILKK(SEQ ID NO:106) which was grown in parallel from the R1 trifunctional amino acid of formula I when R2 is 0 atoms and R1 is a lysine. The resulting synthetic growth modulator analog is of the following specific structure:

and is sometimes called B7A1-K-NS. In the foregoing structure, “Ahx” is 6-amino hexanoic acid, sometimes also called “6-Ahx” or “Hex”. The single letters are standard amino acid single letter abbreviations for the naturally coded amino acids.

example 3

[0192]A compound of the present invention is synthesized by solid phase peptide chemistry with the general structure of formula I wherein X is a BMP-2 receptor binding amino acid sequence having the sequence ISMLYLDENEKVVLKNY(SEQ ID NO:30) grown in parallel from an R1 trifunctional amino acid of formula I and wherein R1 is lysine. The resulting synthetic growth modulator analog is of the following specific structure:

[0193]In the foregoing structure, “Ahx” is 6-amino hexanoic acid, sometimes also called “6-Ahx” or “Hex”. The single letters are standard amino acid single letter abbreviations for the naturally coded amino acids.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Molar densityaaaaaaaaaa
Molar densityaaaaaaaaaa
Timeaaaaaaaaaa
Login to View More

Abstract

A heparin-binding growth factor (HBGF) analog having two substantially similar sequences (homodimeric sequences) branched from a single amino acid residue, where the sequences are analogs of a particular HBGF that binds to a heparin-binding growth factor receptor (HBGFR), or alternatively that bind to a HBGFR without being an analog of any particular HBGF. The homodimeric sequences may be derived from any portion of a HBGF. The synthetic HBGF analog may be an analog of a hormone, a cytokine, a lymphokine, a chemokine or an interleukin, and may bind to any HBGFR. Further provided are preparations for medical devices, pharmaceutical compositions and methods of using the same.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to and the benefit of the filing of U.S. Provisional Patent Application Ser. No.60 / 655,570 entitled “Single Branch Heparin Binding Growth Factor” filed on Feb. 22, 2005 and the specification and claims thereof are incorporated herein by reference.INTRODUCTION[0002]The invention relates to the field of synthetic peptides and analogs of heparin-binding growth factors, including homodimeric synthetic heparin-binding growth factor analogs wherein two sequences are branched from a single branch point, the single branch point including at least one trifunctional amino acid residues, which branch point is further covalently bonded to a heparin-binding sequence. The invention further relates to the clinical uses of such analogs as soluble drugs and as coatings for medical devices.BACKGROUND OF THE INVENTION[0003]Note that the following discussion refers to a number of publications by author(s) and year of publicat...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K38/18A61K38/02
CPCC07K14/49A61K38/00C07K14/522C07K14/51A61P1/04A61P17/00A61P35/00A61P43/00
InventorTAKAHASHI, KAZUYUKIZAMORA, PAUL O.
OwnerBIOSURFACE ENG TECH