| Abstract
| - Three analogues of RA-VII (1), an antitumor bicyclic hexapeptide from Rubia plants, weresynthesized. Three analogues, [Gly-1]RA-VII (4), [Gly-2]RA-VII (5), and [Gly-4]RA-VII (6), in whichone of the three alanine residues in 1 was replaced by a glycine residue, were prepared by linkingof the cycloisodityrosine unit, obtained by degradation of 1, to three different glycine-containingtetrapeptides followed by macrocyclization. Of these three analogues, analogue 4 showed the highestcytotoxic activity. The NMR study revealed that in solution the conformer structures and theirratios of analogue 4 were very similar to those of natural peptide 1, suggesting that the methylgroups at Ala-2 and Ala-4 should be essential for producing the bioactive conformation, whereasthat at d-Ala-1 is not essential.
|
