Sachiyuki Hamano

Discovery and development of aryl-fused imidazole-based angiotensin II antagonists

Abstract A phenolic benzofuran derivative 1 was identified as an angiotensin II receptor antagonist by random screening. Structural modifications led to a novel series of N-(4-hydroxyphenylmethyl)benzimidazoles and imidazo[4,5-b]pyridines, some of which inhibited angiotensin II-induced contractions in rabbit aortic strips with pA2 values of nearly 9. The related biphenylmethyl derivative E4177 showed potent and long-lasting activity in vivo.

Production and characterization of monoclonal antibodies against particulate guanylate cyclase in porcine kidney

Three monoclonal antibodies (Ig G1 type) to particulate guanylate cyclase from porcine kidney cortex have been produced by fusing spleen cells from immunized BALB/c mouse with P3X63 myeloma cells. The antibodies were detected by their ability to bind immobilized antigen and by immunoprecipitation of enzyme activity. After subcloning by limiting dilution, hybridomas were injected intraperitoneally into mice to produce ascitic fluid. The antibodies recognized a 180,000 dalton protein in Lubrol-PX extract of porcine kidney cortex membrane, and when immobilized on Sepharose 4B, they co-precipitated both [125I]human atrial natriuretic peptide (ANP)-receptor complex and guanylate cyclase activity. The antibodies caused a greater increase in generation of cGMP than that of ANP.