title: A non-hemorrhagic hybrid heparin/heparan sulfate with anticoagulant potential.
abstract: The structural characterization and the anticoagulant potential of a novel heparin/heparan sulfate-like compound from the heads of Litopenaeus vannamei shrimp are described. While it is distinct from either heparin or heparan sulfate, enzymatic depolymerization and nuclear magnetic resonance spectroscopy analyses revealed that this molecule does share some structural features with heparin, such as the high degree of N- and 6-O-sulfation and minor N-acetylation, and with heparan sulfate, in the glucuronic acid content. Its ability to stabilize human antithrombin explains its significant anticoagulant activity in aPTT and Factor-Xa inhibition assays. Interestingly, in contrast to mammalian heparin, the shrimp compound displayed negligible hemorrhagic effect. Together, these findings have particular interest since they reveal a novel molecule with significant anti-Xa activity coupled with low bleeding effects which make the shrimp heparin/HS-like compound a potential alternative for mammalian heparin.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Faculdade de Ciências da Saúde do Trairi, Universidade Federal do Rio Grande do Norte, Santa Cruz, RN, Brazil.
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Brito
authors.forename: Rômulo S
authors.initials: RS
authors.lastname: Cavalcante
authors.forename: Lais C G F
authors.initials: LC
authors.lastname: Palhares
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Hughes
authors.forename: Giulianna P V
authors.initials: GP
authors.lastname: Andrade
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Yates
authors.forename: Helena B
authors.initials: HB
authors.lastname: Nader
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Lima
authors.forename: Suely F
authors.initials: SF
authors.lastname: Chavante
mesh_terms: D000107:Acetylation; D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000991:Antithrombins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification; D002417:Cattle; D002852:Chromatography, Ion Exchange; D015951:Factor Xa / Q000737:chemistry; D065427:Factor Xa Inhibitors; D020723:Glucuronic Acid / Q000737:chemistry; D006257:Head; D006470:Hemorrhage / Q000517:prevention & control*; D006493:Heparin / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006497:Heparan Sulfate / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007422:Intestines / Q000737:chemistry; D010179:Pancreas / Q000737:chemistry; D010314:Partial Thromboplastin Time; D033561:Penaeidae / Q000737:chemistry*; D051381:Rats; D013552:Swine; D013623:Tail / Q000098:blood supply / Q000187:drug effects
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D015951:Factor Xa; D065427:Factor Xa Inhibitors; D020723:Glucuronic Acid; D006493:Heparin; D006497:Heparan Sulfate
keywords: Anticoagulant; Antithrombin; Hemorrhagic activity; Heparan sulfate; Heparin; Thermostabilization