The enormous importance of peptidal hormone and neurotransmitter agonists and antagonists and of peptidal inhibitors of proteolytic enzymes is well understood. However, peptides are rapidly degraded in vivo by exo and endo peptidases. Another shortcoming of peptides as potential therapeutic agents is their lack of bioavailability by the oral route. The latter deficiency appears to be due in part to the amide backbone. We propose to synthesize novel mimics of peptide hormone agonists/antagonists which are devoid of the amide backbone. The side chains are to be retained in the appropriate spatial disposition. In the case the enzyme inhibitor mimics, provision is also made for H-bonding interactions with the enzyme backbone. Such H-bonding is not required for the interaction of hormone agonist/antagonist with their receptors. The proposed synthetic targets relate to the hormone somatostatin, the proteolytic enzyme renin, and therefore also to other aspartate proteases, notably the HIV protease of importance in AIDS.
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