Single branch heparin-binding growth factor analogs

US20080227696A1Inactive Publication Date: 2008-09-18BIOSURFACE ENG TECH
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  • Single branch heparin-binding growth factor analogs
  • Single branch heparin-binding growth factor analogs
  • Single branch heparin-binding growth factor analogs

Examples

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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.

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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

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Application Information

Patent Timeline
18 Sep 2008
Publication
US20080227696A1
IPC
A61K38/18; A61K38/02
CPC
C07K14/49; A61K38/00; C07K14/522; C07K14/51; A61P1/04; A61P17/00; A61P35/00; A61P43/00
Inventors
TAKAHASHI, KAZUYUKI; ZAMORA, PAUL O.