The angiotensin I converting enzyme and aminopeptidase B inhibitory properties of key analogs of K-13 and OF4949, constituting key partial structures or substructures of the natural products, are detailed in studies to define the essential pharmacophores.K-13 (1), an isodityrosine derived cyclic peptide isolated from Micromonosporo halophyticu subsp. exilisiu K-13 and identified in spectroscopic and chemical degradative studies, has been shown to be a potent noncompetitive inhibitor of angiotensin I converting enzyme (40 = 0.17 pg/mL. K = 0.35 pM) and a weak inhibitor of aminopeptidase B. K-13 represents the newest member of a class of isodityrosine derived cyclic peptides including OF4949-I - IV (2-S), pipemzinomycin, bouvardin and related agents. OF4949-I - IV were found to be potent inhibitors of aminopeptidase B, to lack conventional cytotoxic activity, and to possess confirmed antitumor activity. Thus, the agents may constitute a new and potentially useful class of antitumor agents that act as immunopotentiators and which may not display host antigenicity or toxicity. Consequently, in the course of synthetic studies on the isodityrosine derived agents, we have prepared a range of key analogs of K-13 and OF4949 constituting key partial structures or substructures. Herein, we report the angiotensin I converting enzyme and aminopeptidase B inhibitory properties of a selected set of the agents (7-29) and their in vitro cytotoxic activity in studies which further define the essential and potentiating structural features that contribute to their biological activity.