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The tridecapeptide neurotensine has been the subject of increased interest since its discovery and characterization in the brain1). Aspects of its pharmacology include physiological effects both in the periphery and the central nervous system2). In order to elucidate further its pathophysiological role, neurotensin agonists and antagonists are needed. In the course of our screening program to find substances that displace the neurotensin from its receptor, a receptor binding assay using guinea-pig brain membranes was performed according to GOEDERT et al.3). During this screening, RP 66453 was isolated as a novel secondary metabolite produced by an Actinomycetes strain. For the production of this compound the Streptomyces strain A 9738 was inoculated into a 2 liter Erlenmeyer flask containing 250ml of seed medium consisting of peptone 0.5%, yeast extract 0.5%, corn steep 0.5%, glucose 1.5%, CaCO3 0.3%, NaCl 0.5% and agar 0.1%.

Isolation of RP 66453, a New Secondary Peptide Metabolite from Streptomyces sp. Useful as a Lead for Neurotensin Antagonists.