Analogs of viroidin. Synthesis of four virotoxin-like F-actin binding heptapeptides with one less hydroxyl group in the dihydroxy-proline ring.
The vitroxins, toxic cyclic heptapeptides from Amanita virosa fungi, contain a 3,4-dihydroxy-L-proline, an imino acid scarcely accessible in greater amounts. Therefore in the syntheses of the analogs described this imino acid was replaced by 4-cis-hydroxy-L-proline, a component of the analogously toxic phallotoxins. The following syntheses are described: 1a = cyclo (L-alanyl-D-threonyl-D-seryl-L-4-cis-hydroxy-L-prolyl-L-alanyl-2- methylthio-L-tryptophyl-L-leucyl), 1b = 1a but with 2-methylsulfonyl-L-tryptophan in position 6, 2a = cyclic (L-valyl-D-threonyl-D-seryl-4-cis-hydroxy-L-prolyl-L-alanyl-2- methylthio-L-tryptophyl-hydroxyl-L-leucyl), and 2b = 2a, but with 2-methylsulfonyl-L-tryptophan in position 6. In a test for binding strength to rabbit muscle F-actin 2b and 2a exhibited about 40% of that of demethylphalloin. Analogs 1a and 2b have not been tested.
D000199:Actins / Q000378:metabolism*; D000546:Amanitins / Q000138:chemical synthesis*; D002855:Chromatography, Thin Layer; D007202:Indicators and Reagents; D009183:Mycotoxins / Q000138:chemical synthesis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D011485:Protein Binding; D013329:Structure-Activity Relationship
D000199:Actins; D000546:Amanitins; D007202:Indicators and Reagents; D009183:Mycotoxins; D010456:Peptides, Cyclic