MAMMALIAN RECOMBINANT COAGULATION PROTEINS - STRUCTURE AND FUNCTION

Recombinant DNA technology has permitted the production of synthetic p roteins which are potentially free of human infectious agents. Despite production in foreign cells, these proteins are structurally and func tionally comparable to the native proteins. Recombinant clotting facto rs VIII, IX, VIIa, and von Willebrand factor have the same primary seq uence as their plasma counterparts. The secondary and tertiary structu res are similar, Post-translational modifications, including proteolyt ic processing, disulfide bonding, addition and processing of N- and O- linked glycans, gamma-carboxylation of glutamic acid residues, beta-hy droxylation of aspartic acid residues, sulfation of tyrosine residues, and phosphorylation of serine residues, are similar but not always id entical, In some instances. these differences may cause significant fu nctional differences. For example, reduced tyrosine sulfation and seri ne phosphorylation of recombinant factor IX have been correlated with reduced recovery following intravenous infusion. The specific clotting activity of the recombinant factors, an indication of their coagulant function, is equivalent to that of the plasma factors. Finally, these proteins have been used clinically and shown to correct clinical defi ciencies of these proteins in a manner that is similar to replacement with plasma factors. All in all, the promise of recombinant DNA techno logy for coagulation and other disorders remains bright. (C) 1998 Else vier Science Ltd. All rights reserved.