Synthesis and in vitro hydroxyapatite binding of peptides conjugated to calcium-binding moieties

Biomacromolecules. 2007 Jul;8(7):2237-43. doi: 10.1021/bm070121s. Epub 2007 May 27.

Abstract

To confer bone-binding properties to proteins and other biological agents that lack specific targeting capacity, model peptide-based molecules were synthesized containing poly(aspartic acid), poly(glutamic acid), or a bisphosphonate (pamidronate). These motifs have well-documented affinities to hydroxyapatite, a property desirable for the targeting of molecules to bone for drug delivery and tissue engineering applications. Model peptides of increasing molecular mass (5-33 amino acids) were directly conjugated to eight aspartic acids (Asp8), eight glutamic acids (Glu8), or pamidronate, purified by high-performance liquid chromatography, and characterized by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectroscopy. The modified peptides were incubated with hydroxyapatite in phosphate-buffered saline at physiological conditions over 24 h. This study revealed a significant amount (>90%) of conjugated peptides adsorbed to the hydroxyapatite as compared to unmodified peptides (<5%). It was found that while there were significant differences between the different hydroxyapatite-binding and control groups for all time points, the size of the peptide had no statistical effect on peptide-hydroxyapatite binding. These results demonstrate that bisphosphonate and oligopeptide conjugates hold great promise for the development of new bioactive molecules for bone-specific applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Calcium / chemistry*
  • Diphosphonates / chemistry
  • Durapatite / chemical synthesis*
  • Durapatite / chemistry
  • Peptides / chemistry*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tissue Engineering

Substances

  • Diphosphonates
  • Peptides
  • Durapatite
  • Calcium