S-deoxo-Abu1, Ile3-amaninamide, an inactive amatoxin analogue

The title compound 3, an amatoxin analogue containing l-α-aminobutyric acid instead of l-asparagine in position 1, as in natural toad stool peptides, has been synthesized. It does not inhibit the eukaryotic DNA-dependent RNA polymerase form II (or B) in concentrations up to 10-4M, whereas 50% inhibition is exerted in M solution by the corresponding Asn-analogue S-deoxo-Ile3-amaninamide 2. The striking difference seems to be due to a relatively small variation of the conformation recognized by sensitive NMR spectroscopic methods.