title: Parathyroid hormone is a heparin/polyanion binding protein: binding energetics and structure modification.
abstract: The interaction of four representative polyanions with parathyroid hormone (PTH) residues 1-84 has been investigated utilizing a variety of spectroscopic and calorimetric techniques. Each of the polyanions employed demonstrate enthalpically driven binding to PTH (1-84) with significant affinity. The polyanions heparin, dextran sulfate, phytic acid, and sucrose octasulfate induce alpha-helical structure in PTH to varying extents depending on the ratio of polyanion to protein employed. Intrinsic and extrinsic fluorescence spectroscopy suggests significant protein tertiary structure alteration upon polyanion binding. Although structural modification occurred upon polyanion binding, PTH colloidal stability was increased depending on the ratio of polyanion to protein used. Nevertheless, the bioactivity of PTH in the presence of various ratios of heparin was not altered. The potential biological significance of PTH/polyanion interactions is discussed.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Kamerzell
authors.forename: Sangeeta B
authors.initials: SB
authors.lastname: Joshi
authors.forename: Donald
authors.initials: D
authors.lastname: McClean
authors.forename: Lori
authors.initials: L
authors.lastname: Peplinskie
authors.forename: Karen
authors.initials: K
authors.lastname: Toney
authors.forename: Damon
authors.initials: D
authors.lastname: Papac
authors.forename: Meili
authors.initials: M
authors.lastname: Li
authors.forename: C Russell
authors.initials: CR
authors.lastname: Middaugh
mesh_terms: D002151:Calorimetry; D016264:Dextran Sulfate / Q000737:chemistry / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000737:chemistry / Q000378:metabolism*; D010833:Phytic Acid / Q000737:chemistry / Q000378:metabolism; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence; D013395:Sucrose / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
chemical_list: D016264:Dextran Sulfate; D006493:Heparin; D010281:Parathyroid Hormone; D010833:Phytic Acid; D000071228:Polyelectrolytes; D011108:Polymers; D013395:Sucrose; C053081:sucrose octasulfate