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BIOPHARMACEUTICALS BIOCHEMISTRY AND BIOTECHNOLOGY - PART 8

Antithrombin antithrombin, đã được đề cập trong bối cảnh của heparin, là chất ức chế tự nhiên dồi dào nhất xảy ra đông máu. Đó là một chuỗi 432 glycoprotein axit amin hiển thị bốn oligosaccharide phụ dây chuyền và một khối lượng phân tử khoảng 58 kDa. Nó hiện diện trong huyết tương ở nồng độ 150 mg / ml và là một chất ức chế mạnh của thrombin (yếu tố IIa) cũng như các yếu tố IXa và Xa | BLOOD PRODUCTS AND THERAPEUTIC ENZYMES 379 major added excipient. The product which displays a useful shelf-life of 2-years when stored at room temperature is reconstituted with saline or water for injections immediately prior to its i.v. administration. A second recombinant product trade name Revasc also produced in S. cerevisiae has also been approved. Antithrombin Antithrombin already mentioned in the context of heparin is the most abundantly occurring natural inhibitor of coagulation. It is a single-chain 432 amino acid glycoprotein displaying four oligosaccharide side-chains and an approximate molecular mass of 58 kDa. It is present in plasma at concentrations of 150 mg ml and is a potent inhibitor of thrombin factor IIa as well as factors IXa and Xa. It inhibits thrombin by binding directly to it in a 1 1 stoichiometric complex. Plasma-derived anti-thrombin AT concentrates have been used medically since the 1980s for the treatment of hereditary and acquired AT deficiency. Hereditary genetic deficiency is characterized by the presence of little no native antithrombin activity in plasma and results in an increased risk of inappropriate blood clot embolus formation. Acquired AT deficiency can be induced by drugs e.g. heparin and oestrogens liver disease which causes decreased AT synthesis or various other medical conditions. Recombinant AT has been successfully expressed in engineered CHO cells. Commercial production via this route however is rendered unattractive due to high relative production costs and to a lesser extent by the scale of production needed to satisfy market demand. Recombinant AT has been produced more economically in the milk of transgenic goats Chapter 3 and this product is currently undergoing clinical trials Figure 9.16 . The recombinant product displays an identical amino acid sequence to that of native human AT although its oligosaccharide composition does vary somewhat from the native protein. Ceprotin human protein C concentrate is an .