Synthesis of biologically active retroenantiomers of angiotensin peptides

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Abstract
The effect of the reversal of the direction of amide bonds in the peptide chain of angiotensin was determined by the synthesis and study of retroenantiomers of the following peptides: 1, [Val5]angiotensin II (angiotensin); 2, [Suc1]angiotensin (desamino-angiotensin); 3, [Ala7]desamino-angiotensin; 4 [.beta.-Ala7]desamino-angiotensin. In all of these retroenantiomers, the N-terminal Phe residue was replaced by a benzylmalonyl moiety in order to maintain the topological features of angiotensin''s C terminus which are important for biological activity. The separation of the diastereomeric peptides containing D- or L-benzylmalonyl residues was possible in the cases of the retroenantiomers of 1 and 2 but not in those of 3 and 4. The retroenantiomers of 1 and 2 were devoid of smooth muscle contracting activities, while those of 3 and 4 contracted the isolated guinea-pig ileum and rat uterus with activities ranging from 8 to 24%, when compared with the respective parent compounds. The sense of the peptide bonds in angiotensin''s backbone is not essential for activity, and the Pro7 residue in angiotensin is important for maintaining an active conformation of the molecule.

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