2-Amino-5-methyl-5-hexenoic acid

2-Amino-5-methyl-5-hexenoic acid (AMHA), a new methionine analog, was isolated from a fermentation broth of Streptomyces sp. MF374-C4 based on its reversal of the effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in a test system that determines the size of growth zones of revertants (His+) of Salmonella typhimurium TA1535. AMHA also inhibited growth of the tester strain in a synthetic medium. These AMHA activities were abolished by methionine. The incidence of spontaneous streptomycin-resistant mutations of Escherichia coli K12 was not decreased by AMHA at concentrations where cell growth was partially inhibited. AMHA inhibited protein synthesis but not DNA or RNA synthesis in S. typhimurium TA1535 and E. coli K-12. The analog inhibited formation of methionyl-tRNA but not of valyl-tRNA in a cell-free system of E. coli, and supported ATP-PPi exchange in the cell-free system. At concentrations where it inhibited cell growth, AMHA decreased the number of foci, induced by ROUS sarcoma virus, on cultured sheets of chick-embryo fibroblasts. The effects of AMHA on focus formation and on the cell growth were overcome by methionine.

From a collection of marine cyanobacteria made in the Coiba National Park along the Pacific coast of the Republic of Panama a novel cyclic depsipeptide, given the trivial name medusamide A, has been isolated and fully characterized. Medusamide A contains four contiguous β-amino acid (2R,3R)-3-amino-2-methylhexanoic acid (Amha) residues. This is the first report of multiple Amha residues and contiguous β-amino acid residues within a single cyclic peptide-type natural product. Stereochemical assignment of the Amha residues was completed following the synthesis of reference standards for this β-amino acid and the subsequent derivatization with Marfey's reagent and LC-MS analysis.