title: Separation of latent, prelatent, and native forms of human antithrombin by heparin affinity high-performance liquid chromatography.
abstract: Latent antithrombin (LAT) is a partially denatured form of human antithrombin (AT). LAT does not inhibit clotting of the blood, but has previously been shown to inhibit angiogenesis and carcinogenesis. Another probably partially denatured form is the so-called prelatent AT (P-LAT), described by Larsson et al. [J. Biol. Chem. 276 (2001) 11996]. In the present work, an analytical heparin affinity chromatography method is described that separates an AT form, which is formed during the pasteurization process and which we believe to be identical to the previously described P-LAT, from native AT and LAT. Non-pasteurized AT was shown to contain no P-LAT, while four, heat-treated commercial AT products all contained P-LAT (1-6%, mean=4%). P-LAT has a slightly lower affinity to heparin than does native AT, but exhibits a much stronger heparin affinity when compared to LAT. P-LAT and native AT were shown to have very similar thrombin inhibiting activity, while LAT lacks such activity.
authors.affiliation: Octapharma AB, SE-11275 Stockholm, Sweden. goran.karlsson@octapharma.se
authors.forename: Göran
authors.initials: G
authors.lastname: Karlsson
authors.forename: Stefan
authors.initials: S
authors.lastname: Winge
mesh_terms: D000991:Antithrombins / Q000302:isolation & purification* / Q000378:metabolism; D002846:Chromatography, Affinity / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D011489:Protein Denaturation; D013997:Time Factors
chemical_list: D000991:Antithrombins; D006493:Heparin