Interactions of cryptolepine and neocryptolepine with unusual DNA structures.
Cryptolepine, the main alkaloid present in the roots of Cryptolepis sanguinolenta, presents a large spectrum of biological properties. It has been reported to behave like a DNA intercalator with a preference for GC-rich sequences. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of cryptolepine and neocryptolepine for DNA structures among duplexes, triplexes, quadruplexes and single strands. Our data confirm that cryptolepine and neocryptolepine prefer GC over AT-rich duplex sequences, but also recognize triplex and quadruplex structures. These compounds are weak telomerase inhibitors and exhibit a significant preference for triplexes over quadruplexes or duplexes.
Guittat
Lionel
L
Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM UR 565, CNRS UMR 8646, 43, rue Cuvier, 75231 Paris cedex 5, France.
Alberti
Patrizia
P
Rosu
Frédéric
F
Van Miert
Sabine
S
Thetiot
Emilie
E
Pieters
Luc
L
Gabelica
Valérie
V
De Pauw
Edwin
E
Ottaviani
Alexandre
A
Riou
Jean-François
JF
Mergny
Jean-Louis
JL
D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D031106:Cryptolepis / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D026121:Indole Alkaloids; D007211:Indoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013058:Mass Spectrometry; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D019098:Telomerase / Q000187:drug effects
D000470:Alkaloids; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D007211:Indoles; D011804:Quinolines; C414982:neocryptolepine; C024015:cryptolepine; D004247:DNA; D019098:Telomerase