title: Identification of a novel structure in heparin generated by potassium permanganate oxidation.
abstract: The worldwide heparin contamination crisis in 2008 led health authorities to take fundamental steps to better control heparin manufacture, including implementing appropriate analytical and bio-analytical methods to ensure production and release of high quality heparin sodium product. Consequently, there is an increased interest in the identification and structural elucidation of unusually modified structures that may be present in heparin. Our study focuses on the structural elucidation of species that give rise to a signal observed at 2.10 ppm in theN-acetyl region of the1H NMR spectrum of some pharmaceutical grade heparin preparations. Structural elucidation experiments were carried out using homonuclear (COSY, TOSCY and NOESY) and heteronuclear (HSQC, HSQC-DEPT, HMQC-COSY, HSQC-TOCSY, and HMBC) 2D NMR spectroscopy on both heparin as well as heparin-like model compounds. Our results identify a novel type of oxidative modification of the heparin chain that results from a specific step in the manufacturing process used to prepare heparin.
authors.affiliation: Momenta Pharmaceuticals, 675 West Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Beccati
authors.affiliation: Momenta Pharmaceuticals, 675 West Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Sucharita
authors.initials: S
authors.lastname: Roy
authors.affiliation: Momenta Pharmaceuticals, 675 West Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Momenta Pharmaceuticals, 675 West Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Nur Sibel
authors.initials: NS
authors.lastname: Gunay
authors.affiliation: Momenta Pharmaceuticals, 675 West Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Ishan
authors.initials: I
authors.lastname: Capila
authors.affiliation: Momenta Pharmaceuticals, 675 West Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Lech
authors.affiliation: Departments of Chemistry and Chemical Biology, Biology, and Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Center for Biotechnology and Interdisciplinary Studies, 110 8th Street, Troy, NY 12180, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.affiliation: Momenta Pharmaceuticals, 675 West Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Venkataraman
keywords: 1H NMR; HSQC; Heparin; N-Acetylglucosamine; Oxidation; Permanganate; Reducing end