Karlsson Göran, Winge Stefan
Octapharma AB, SE-11275 Stockholm, Sweden.
Protein Expr Purif. 2004 Feb;33(2):339-45. doi: 10.1016/j.pep.2003.10.008.
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.
潜在抗凝血酶（LAT）是人类抗凝血酶（AT）的一种部分变性形式。LAT不抑制血液凝固，但先前已证明其可抑制血管生成和癌变。另一种可能的部分变性形式是所谓的前潜在AT（P-LAT），由拉尔森等人描述[《生物化学杂志》276（2001）11996]。在本研究中，描述了一种分析性肝素亲和色谱法，该方法可将在巴氏灭菌过程中形成的一种AT形式（我们认为其与先前描述的P-LAT相同）与天然AT和LAT分离。未经过巴氏灭菌的AT被证明不含P-LAT，而四种经过热处理的商业AT产品均含有P-LAT（1%-6%，平均为4%）。P-LAT对肝素的亲和力略低于天然AT，但与LAT相比，其对肝素的亲和力要强得多。P-LAT和天然AT具有非常相似的凝血酶抑制活性，而LAT缺乏这种活性。
