title: On the catalysis of calcium oxalate dihydrate formation by osteopontin peptides.
abstract: Inhibition of calcium oxalate monohydrate (COM) formation and initiation of the dihydrate (COD) phase by osteopontin (OPN) have been proposed to play an important role in preventing kidney stone formation. We have studied the roles of OPN phosphate and carboxylate groups in the modulation of calcium oxalate (CaOx) crystallization using synthetic peptides corresponding to residues 65-80, 129-144, 220-235 and 273-288 of rat OPN. We investigated the effects of these peptides (0-20 μg/ml) on COM and COD formation by correlating qualitative and quantitative microscopic data with the physicochemical characteristics of the peptides used. In general, highly acidic/hydrophilic peptides strongly inhibit COM and promote COD formation. However, OPN129-144, which is basic, and OPN273-288, which is only slightly acidic, also induced COD precipitation. It is likely that inhibition of nucleation and/or growth of COM by OPN peptides maintains a high supersaturation, thereby allowing formation of the more-soluble dihydrate polymorph. In addition, growth of COD from the substrate in <100>/<110> directions suggests that highly acidic OPN peptides may nucleate crystals from the Ca(2+)-rich {100}/{110} faces. At higher peptide concentrations, however, peptides containing either phosphates or contiguous carboxylates inhibit COD, whereas peptides containing both promote COD formation further.
authors.affiliation: Department of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada. brian.chan@queensu.ca
authors.forename: Brian P H
authors.initials: BP
authors.lastname: Chan
authors.forename: Krista
authors.initials: K
authors.lastname: Vincent
authors.forename: Gilles A
authors.initials: GA
authors.lastname: Lajoie
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Goldberg
authors.forename: Bernd
authors.initials: B
authors.lastname: Grohe
authors.forename: Graeme K
authors.initials: GK
authors.lastname: Hunter
mesh_terms: D000595:Amino Acid Sequence; D002129:Calcium Oxalate / Q000737:chemistry*; D002384:Catalysis; D011232:Chemical Precipitation / Q000187:drug effects; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D057927:Hydrophobic and Hydrophilic Interactions; D007526:Isoelectric Point; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D053495:Osteopontin / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D010455:Peptides; D053495:Osteopontin; D002129:Calcium Oxalate