Conformational analysis of heparin binding peptides

Conformational analysis of heparin binding peptides
Received 23 June 2004; accepted 9 September 2004. Available online 28 October 2004.
Manuela Vacatelloa, , , Gabriella DÇƒÙAuriaa, b, Lucia Falcignoa, b, Monica Dettinc, Roberta Gambarettoc, Carlo Di Belloc and Livio Paolilloa, b
Biomaterials
Volume 26, Issue 16 , June 2005, Pages 3207-3214
ScienceDirect
aDepartment of Chemistry, University of Naples Çƒ?Federico IIÇƒ?, Complesso Universitario di Monte S. Angelo, via Cintia-80126 Naples, Italy
bInstitute of Biostructure and Bioimaging, CNR, via Mezzocannone 6-80134 Naples, Italy
cDepartment of Chemical Process Engineering, University of Padua, via Marzolo 9, 35131 Padua, Italy
Abstract
A properly engineered biomaterial for dental/orthopaedic applications must induce specific responses from the osteoblasts at the implant site. A most desirable response is an efficient adhesion, as it represents the first phase in the cell/material interaction and the quality of this phase will influence the cell's capacity to organize into a new functional tissue. The four osteoblast-adhesive peptides discussed in this paper are mapped on the 339ÇƒÏ364 sequence (339MAPRPSLAKKQRFRHRNRKGYRSQRG364) located in the primary heparin-binding site of human vitronectin (HVP). Adsorbed on a polystyrene scaffold, these peptides display different adhesive activities towards osteoblasts. In this paper we report on the structural analysis in solution of the peptides through NMR and computational techniques. We find that the peptides with the highest adhesive activities display a hydrophobic patch opposite to the charged surface candidate to interact with heparin. These findings suggest that the peptides might adsorb on the polystyrene support in a favourable orientation for their activity. Furthermore, molecular models obtained for the four peptides in solution were used in rigid docking simulations with a heparin model. Assuming that the peptide solution conformations are not very different from the polystyrene-adsorbed structures, the simulations reveal that peptide adhesive activity is also affected by the number of ionic interactions and spacing between charged residues.
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