title: Phosphorylation of osteopontin peptides mediates adsorption to and incorporation into calcium oxalate crystals.
abstract: Phosphorylated peptides of osteopontin (OPN) have been shown to inhibit the growth of the {100} face of calcium oxalate monohydrate (COM). The inhibitory potency has been shown to be dependent on the phosphate content of the peptide. The purpose of this study is to better understand the means by which phosphate groups promote crystal growth inhibition by OPN peptides. Peptides of rat bone OPN 220-235 peptides have been synthesized with zero (P0), 1 (P1) or 3 (P3) phosphate modifications. COM crystals were grown in the presence of 0.1-10 microg of P0, P1 or P3. P0 incorporation into COM crystals was evident at 10 microg/ml of peptide, whereas the phosphorylated peptides P1 and P3 were incorporated at all tested concentrations. At 5 microg/ml of P3, COM crystals exhibited a 'dumbbell' morphology. To study the peptide-mineral interaction, surface frequency plots were constructed from molecular dynamics simulations of OPN peptide adsorption. Carboxylate and phosphate groups were found to adsorb in specific orientations to the COM {100} surface. In conclusion, it appears that the phosphate groups on OPN peptides are capable of interacting with the COM {100} surface. This interaction appears to increase the adsorption energy of the peptide to the surface, thus enhancing its inhibitory potency.
authors: School of Dentistry and CIHR Group in Skeletal Development and Remodeling, University of Western Ontario, London, Ont., Canada.
authors: Jason
authors: J
authors: O'Young
authors: Sara
authors: S
authors: Chirico
authors: Nehal
authors: N
authors: Al Tarhuni
authors: Bernd
authors: B
authors: Grohe
authors: Mikko
authors: M
authors: Karttunen
authors: Harvey A
authors: HA
authors: Goldberg
authors: Graeme K
authors: GK
authors: Hunter
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D000818:Animals; D002129:Calcium Oxalate / Q000737:chemistry*; D003198:Computer Simulation; D003460:Crystallization; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D053495:Osteopontin / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D013499:Surface Properties
chemical_list: D010455:Peptides; D053495:Osteopontin; D002129:Calcium Oxalate