Prev. Article Next Article Table of Contents

Article

Synthesis and in Vitro Hydroxyapatite Binding of Peptides Conjugated to Calcium-Binding Moieties

Matthew B. Murphy,^† Jeffrey D. Hartgerink,^†^‡ Achim Goepferich,^§ and Antonios G. Mikos*^†

Departments of Bioengineering, MS 142, and Chemistry, MS 60, Rice University, Post Office Box 1892, Houston, Texas 77251-1892, and Department of Pharmaceutical Technology, University of Regensburg, Regensburg, Germany 93040

Biomacromolecules, 2007, 8 (7), pp 2237–2243

DOI: 10.1021/bm070121s

Publication Date (Web): May 27, 2007

†

Department of Bioengineering, Rice University.

‡

Department of Chemistry, Rice University.

University of Regensburg.

Author to whom correspondence should be addressed: tel 713-348-5355; fax 713-348-4244; e-mail mikos@rice.edu.

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.

View: Full Text HTML | Hi-Res PDF