Lactam restriction of peptide conformation in cyclic hexapeptides which alter rumen fermentation

gamma, delta- and epsilon-lactam containing cyclic hexapeptide analogs of cyclo-(Ala-Sar)3 have been prepared by cyclotrimerization. The analogs are covalently bridged between the methyl groups of the alanine and sarcosine residues. Only the delta-lactam of the S configuration shows the same ability as cyclo-(Ala-Sar)3 to inhibit methane production in the fermentation in rumen stomach fluid. The lactam rings of different size therefore offer a sensitive probe of the bioactive conformation of a peptide.