S-deoxo-Abu1,Ile3-amaninamide, an inactive amatoxin analogue.
The title compound 3, an amatoxin analogue containing L-alpha-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(-4)M, whereas 50% inhibition is exerted in 10(-6)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.
Zanotti
G
G
CNR, Department of Pharmaceutical Sciences, University La Sapienza, Rome, Italy.
Wieland
T
T
D'Auria
G
G
Paolillo
L
L
Trivellone
E
E
D000546:Amanitins / Q000138:chemical synthesis* / Q000494:pharmacology; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors; D013696:Temperature
D000546:Amanitins; C064376:amaninamide, S-deoxo-Abu(1)-Ile(3)-; C018207:amatoxin; D012319:RNA Polymerase II