Siegmund Reißmann

4-Amidinobenzylamine-Based Inhibitors of Urokinase

A series of 4-amidinobenzylamine-based peptidomimetic inhibitors of urokinase was synthesized. The most potent one, benzylsulfonyl-D-Ser-Ala-4-amidinobenzylamide 16, inhibits uPA with a K(i) of 7.7 nM but is less selective than 10 with a Gly as P2 residue. Hydroxyamidine and carbonate prodrugs were prepared, which are rapidly converted into the active inhibitors in rats after subcutaneous application.

Expression and Functional Characterization of a pHis-Tagged Human Bradykinin B2 Receptor in COS-7Cells

Abstract A polyHistagged bradykinin (BK) B[2] receptor (pHis BKR) cDNA was constructed and expressed in COS-7 cells. The pHisBKR is suitable for both immunoprecipitation and immunoblotting with antipolyHis antibodies and can be easily purified using NiNTA columns. Immunochemical detection revealed a molecular mass of approximately 66 kDa. The pHisBKR is capable of mediating BKinduced stimulation of inositol phosphate formation as well as of mitogenactivated protein kinase (MAPK) activity. Compared with the wildtype receptor (WTBKR) the tagged receptor showed a slightly enhanced affinity towards BK but a reduced expression level. Despite these modified pharmacological properties the pHistagged BKR may be a useful tool for studying BKR modifications and signaling.

The Problem of Latency at Bradykinin and Some Analogues

The polypeptide bradykinin possesses a strong characteristical slow smooth muscle stimulating activity. In the most cases its action is evident after a defined period of time — its latency. Because of their latency and the character of contraction bradykinin and angiotensin are signified as typically slow reacting substances in contrast to acetylcholine, histamine and serotonin, which are characterized as fast reacting agents. Eledoisin, a tachykinin, is standing between both groups (Wiegershausen and Deptalla 1969).