title: Heparin's solution structure determined by small-angle neutron scattering.
abstract: Heparin is a linear, anionic polysaccharide that is widely used as a clinical anticoagulant. Despite its discovery 100 years ago in 1916, the solution structure of heparin remains unknown. The solution shape of heparin has not previously been examined in water under a range of concentrations, and here is done so in D2 O solution using small-angle neutron scattering (SANS). Solutions of 10 kDa heparin-in the millimolar concentration range-were probed with SANS. Our results show that when sodium concentrations are equivalent to the polyelectrolyte's charge or up to a few hundred millimoles higher, the molecular structure of heparin is compact and the shape could be well modeled by a cylinder with a length three to four times its diameter. In the presence of molar concentrations of sodium, the molecule becomes extended to nearly its full length estimated from reported X-ray measurements on stretched fibers. This stretched form is not found in the presence of molar concentrations of potassium ions. In this high-potassium environment, the heparin molecules have the same shape as when its charges were mostly protonated at pD ≈ 0.5, that is, they are compact and approximately half the length of the extended molecules.
authors.affiliation: NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD, 20899. rubinson@wright.edu.|Department of Biochemistry and Molecular Biology, Wright State University, Dayton, OH, 45435. rubinson@wright.edu.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Rubinson
authors.affiliation: Department of Pharmaceutical Chemistry, Zhejiang Ocean University, Zhoushan City, Zhejiang Province, People's Republic of China.|Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180.
authors.forename: Yin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180.
authors.forename: Brady F
authors.initials: BF
authors.lastname: Cress
authors.affiliation: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180.
authors.forename: Fuming
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180. linhar@rpi.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D017666:Deuterium Oxide / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D033363:Neutron Diffraction; D053838:Scattering, Small Angle
chemical_list: D006493:Heparin; D017666:Deuterium Oxide
keywords: aqueous solution structure; counter ion concentration effects; heparin; polyelectrolyte collapse; secondary structure