Stephan Henke

DesArg9D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (desArg10-[Hoe140]) is a bradykinin B1 receptor antagonist

Abstract DesArg 9 -D-Arg[Hyp 3 ,Thi 5 ,D-Tic 7 ,Oic 8 ]BK is a potent and stable B 1 bradykinin (BK) receptor antagonist which was one order of magnitude more potent (IC 50 1.2 × 10 −8 M) in the isolated rabbit aorta than the known selective B 1 BK receptor antagonist, desArg 9 -[Leu 8 ]BK (IC 50 1.1 × 10 −7 M). DesArg 9 -D-Arg[Hyp 3 ,Thi 5 ,D-Tic 7 ,Oic 8 ]BK is the desArg 10 derivative of Hoe 140, a new, potent, stable, selective and long-acting B 2 BK receptor antagonist. In B 2 organ preparation it was three orders of magnitude less potent than Hoe140. Since it is potent and stable it could contribute to the investigation of B 1 BK receptor function.

Inhibition of HIV-1 protease by short peptides derived from the terminal segments of the protease

The active HIV-1 protease is a homodimeric enzyme. A beta-sheet consisting of N- and C-terminal segments provides the main driving force for dimerization of the inactive protomers. Several short peptides with sequences derived from the N- and C-termini of the protease were tested for inhibition of protease activity and for inhibition of HIV-1 replication in lymphocytes. Medium inhibitory activity was found with each of the peptides in the enzyme test and no inhibition of the lymphocytes was found up to 200 micrograms/ml. The enzyme tests indicate that HIV-1 protease is the target of the inhibitory action. Synergistic action could not be found with pairs of the peptides derived from the two different termini. Prolonged incubation with one of the peptides increased inhibition indicating a slow dissociation of the protease dimers. No cytotoxic effect of the inhibitors could be found below 200 micrograms/ml.