Luzopeptins consist of two identical, substituted
quinolines linked to a cyclic decadepsipeptide, with a 2-fold symmetry.
Luzopeptin A, with two acetylated sites in its
peptide ring, is active against several experimental animal
tumor systems.
Luzopeptin B (one acetylated site) is less active, and
luzopeptin C (no acetylation) is inactive. Our studies showed that all three
luzopeptins and a half-molecule of
luzopeptin C exhibited similar fluorescence (400 to 700 nm, with a peak at 490 to 496 nm) with an excitation spectrum in the 200 to 450 nm range (with a peak at 250 to 252, 337, and 385 nm). The half-molecule had the strongest fluorescence, followed in order by
luzopeptins A, B, and C.
DNA binding quenched both fluorescence and absorption of
luzopeptins. Studies of the
DNA-induced fluorescence and absorption quenching and the
drug-induced viscosity and gel electrophoretic mobility changes of
DNA suggested that
luzopeptin C was slightly more effective than
luzopeptins B and A in both the bifunctional
DNA intercalation and the
drug-induced
DNA-
DNA intermolecular cross-linking. Thus, the lack of antitumor activity of
luzopeptin C is not the result of the lack of interactions with
DNA. The half-molecule of
luzopeptin C (
quinoline with a pentapeptide) and smaller fragments (
quinoline alone or with one to four
peptide residues) did not react with
DNA. Thus, the planar
quinoline chromophore alone is unable to intercalate with
DNA. The peptidic cyclic structure of
luzopeptins is essential for the bifunctional intercalation of the twin chromophores, probably by providing proper conformational orientations of the chromophores.