Cationic 5,10,15,20-Tetrakis(N-methylpyridinium-4-yl)porphyrin Fully Intercalates at 5'-CG-3' Steps of Duplex DNA in Solution

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• 作者：Anton B. Guliaev and Neocles B. Leontis
• 刊名：Biochemistry
• 出版年：1999
• 出版时间：November 23, 1999
• 年：1999
• 卷：38
• 期：47
• 页码：15425 - 15437
• 全文大小：360K
• 年卷期：v.38,no.47(November 23, 1999)
• ISSN：1520-4995

文摘

The interaction of 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin (T4MPyP⁴⁺) withthe oligonucleotide DNA duplex [d(GCACGTGC)]₂ was studied by two-dimensional ¹H NMRspectroscopy, optical absorbance, circular dichroism, and molecular dynamics simulation employing particlemesh Ewald methods. T4MPyP⁴⁺ is one of the largest aromatic molecules for which intercalative bindingto DNA has been proposed, although this has been called into question by recent X-ray crystallographicwork [Lipscomb et al. (1996) Biochemistry 35, 2818-2823]. T4MPyP⁴⁺ binding to [d(GCACGTGC)]₂produced a single set of (mostly) upfield-shifted DNA resonances in slow exchange with the resonancesof the free DNA. Intra- and intermolecular NOEs observed in the complex showed that the porphyrinintercalates at the central 5'-CG-3' step of the DNA duplex without disrupting the flanking base pairs.Absorption and circular dichroism spectra of the complex also support intercalative binding. Moleculardynamics simulations (using explicit solvent and PME methods), carried out for fully and partiallyintercalated complexes, yielded stable trajectories and plausible structures, but only the symmetrical, fullyintercalated model agreed with NOESY data. Stable hydrogen bonding was observed during 600 ps ofMD simulation for the base pairs flanking the binding site.