Synthesis and evaluation of bis-dipeptide and bis-tripeptide analogues of actinomycin D.
Six-bis-dipeptide analogues of actinomycin D, all containing two threonyl-D-valine side chains, were prepared. Also two bis-tripeptide analogues containing an additional proline or oxoproline residue were synthesized. None of the compounds bound to DNA in a manner similar to actinomycin D. This lack of strong intercalative binding emphasizes the importance of the pentapeptidolactone side chains in the binding of actinomycin D to DNA and also highlights the deficiences inherent in using only small nucleotide sequences in investigating drug-DNA binding. None of the analogues tested showed any antitumor activity, although actinocylbis(threonyl-D-valine methyl ester) did show 10% of the antibacterial activity of actinomycin D vs. Bacillus subtilis.
D000818:Animals; D001412:Bacillus subtilis / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D003609:Dactinomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use; D004151:Dipeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use
D004151:Dipeptides; D009842:Oligopeptides; D003609:Dactinomycin; D004247:DNA