title: Interactions of cryptolepine and neocryptolepine with unusual DNA structures.
abstract: 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.
authors.affiliation: Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM UR 565, CNRS UMR 8646, 43, rue Cuvier, 75231 Paris cedex 5, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Guittat
authors.forename: Patrizia
authors.initials: P
authors.lastname: Alberti
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rosu
authors.forename: Sabine
authors.initials: S
authors.lastname: Van Miert
authors.forename: Emilie
authors.initials: E
authors.lastname: Thetiot
authors.forename: Luc
authors.initials: L
authors.lastname: Pieters
authors.forename: Valérie
authors.initials: V
authors.lastname: Gabelica
authors.forename: Edwin
authors.initials: E
authors.lastname: De Pauw
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ottaviani
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Riou
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mergny
mesh_terms: 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
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D007211:Indoles; D011804:Quinolines; C414982:neocryptolepine; C024015:cryptolepine; D004247:DNA; D019098:Telomerase