title: Conformational analysis of heparin binding peptides.
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 339-364 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.
authors.affiliation: Department of Chemistry, University of Naples Federico II, Complesso Universitario di Monte S. Angelo, via Cintia-80126 Naples, Italy. manuela@chemistry.unina.it
authors.forename: Manuela
authors.initials: M
authors.lastname: Vacatello
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Auria
authors.forename: Lucia
authors.initials: L
authors.lastname: Falcigno
authors.forename: Monica
authors.initials: M
authors.lastname: Dettin
authors.forename: Roberta
authors.initials: R
authors.lastname: Gambaretto
authors.forename: Carlo
authors.initials: C
authors.lastname: Di Bello
authors.forename: Livio
authors.initials: L
authors.lastname: Paolillo
mesh_terms: D000595:Amino Acid Sequence; D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion; D002942:Circular Dichroism; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D007477:Ions; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D011487:Protein Conformation; D011509:Proteoglycans / Q000737:chemistry; D011522:Protons; D012984:Software; D023822:Tissue Engineering / Q000379:methods*; D019096:Vitronectin / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D007477:Ions; D010455:Peptides; D011137:Polystyrenes; D011509:Proteoglycans; D011522:Protons; D019096:Vitronectin; D006493:Heparin