Recombinant proteins having thrombomodulin activity, DNA constructs which encode them, vectors, cells and process for preparing them, pharmaceutical preparations which comprise the proteins, and the use of the proteins for coating /HO The invention comprises a group of compounds which possess thrombomodulin activity defined by a high degree of affinity binding to thrombin and the ability to provide a complex between such a compound and thrombin having the ability to activate protein C, and which comprise, from the C-terminal moiety of the molecule, two or more of the following structural elements: a) a short cytoplasmic domain of approx. 56 amino acids, b) a transmembrane region of approx. 24 amino acids, c) a region which is rich in serine, threonine and proline residues, d) a domain which comprises at least two EGF domains, and e) a N-terminal domain, where one or more of the elements a), b) and/or c) can be omitted or replaced with affinity-imparting units or units which inc

摘要

The invention comprises a group of compounds which possess thrombomodulin activity defined by a high degree of affinity binding to thrombin and the ability to provide a complex between such a compound and thrombin having the ability to activate protein C, and which comprise, from the C-terminal moiety of the molecule, two or more of the following structural elements: a) a short cytoplasmic domain of approx. 56 amino acids, b) a transmembrane region of approx. 24 amino acids, c) a region which is rich in serine, threonine and proline residues, d) a domain which comprises at least two EGF domains, and e) a N-terminal domain, where one or more of the elements a), b) and/or c) can be omitted or replaced with affinity-imparting units or units which increase the solubility in physiological solutions, or physiologically compatible derivatives thereof. In a preferred embodiment, four EGF domains are coupled N- terminally to the signal peptide from human tissue-type plasminogen activator with the aid of an adapter sequence. The proteins can be used for treating and/or preventing thrombic episodes.