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Vol 47(2013) N 3 p. 453-460;
O.A. Kovaleva1,2, A.K. Shchyolkina1, O.K. Mamaeva1, V.A. Olshevskaya3, A.V. Makarenkov3, A.S. Semeikin4, A.A. Shtil5, O.F. Borisov1, D.N. Kaluzhny1*

Complexes of Antiparallel Telomeric G-Quadruplex d(TTAGGG)4 with Carboxymethyl Tetracationic Porphyrins

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Moscow Institute of Physics and Technology (State University), Dolgoprudny, 141700 Russia
3Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, 119991,
4Ivanovo State University of Chemistry and Technology, Ivanovo, 153460 Russia
5Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478 Russia

*uzhny@mail.ru
Received - 2012-12-17; Accepted - 2013-01-14

Porphyrins are a chemical class that is widely used in drug design. Cationic porphyrins may bind to DNA guanine quadruplexes. We report the parameters of the binding of 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium) porphyrin (P1) and 5,10,15,20-tetrakis(N-etoxycarbonylmethyl-4-pyridinium) porphyrin (P2) to antiparallel telomeric G-quadruplex formed by d(TTAGGG)4 sequence (TelQ). The binding constants (Ki) and the number of binding sites (Nj) were determined from absorption isotherms generated from the absorption spectra of complexes of P1 and P2 with TelQ. Compound P1 demonstrated a high affinity to TelQ (K1 = (40 ± 6) 106 М-1, N1 = 1; K2 = (5.4 ± 0.4) 106 М-1, N2 = 2). In contrast, the binding constants of P2-TelQ complexes (K1 = (3.1 ± 0.2) × 106 М-1, N1 = 1; K2 = (1.2 ± 0.2) × 106 М-1, N2 = 2) were one order of magnitude smaller than the corresponding values for P2-TelQ complexes. Measurements of the quantum yield and fluorescence lifetime of the drug's TelQ complexes revealed two types of binding sites for P1 and P2 on the quadruplex oligonucleotide. We concluded that strong complexes can result from the interaction of the porphyrins with TTA loops whereas the weaker complexes are formed with G-quartets. The altered TelQ conformation detected by the circular dichroism spectra of P1-TelQ complexes can be explained by the disruption of the G-quartet. We conclude that peripheral carboxy groups contribute to the high affinity of P1 for the antiparallel telomeric G-quadruplex.

DNA, G-quadruplex, porphyrins, fluorescence, circular dichroism



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