KRINGLE PROTEINS DERIVED FROM HUMAN PROTHROMBIN HAVING INHIBITORY ACTIVITY OF GROWTH OF ENDOTHELIAL CELL

摘要

PURPOSE: Kringle proteins, which have inhibitory effect on endothelial cell growth, abiogenesis, and formation of prothrombinase complex, can be used in treating cancers, rheumatoid arthritis, and diseases caused by blood clotting. CONSTITUTION: Human prothrombin kringle protein-1 and -2 are isolated and purified from hydrolysat of prothrombin protein with factor Xa. The prothrombin protein is isolated from human blood plasma and purified using ion chromatography. Amino acid sequence of N-terminal of purified kringle proteins are confirmed by amino acid sequencing. cDNAs of each kringle protein-1 and -2 are amplified with PCR using human prothrombin as a cDNA template and cloned into expression vector of E.coli. The inhibition activities of kringle proteins are identified by analysis of chick chorioallantoin membrane and growth experiment of BCE cell.