title: [5,10,15,20-Tetra-(N-methyl-3-pyridyl)porphyrin destabilizes the anti-parallel telomeric quadruplex d(TTAGGG)4].
abstract: We studied the parameters of binding of 5,10,15,20-tetra-(N-methyl-3-pyridyl)porphyrin (TMPyP3) to the anti-parallel human telomeric G-quadruplex d(TTAGGG)4, the oligonucleotide dTTAGGGTTAGAG(TTAGGG)2 that does not form a quadruplex structure, as well as to the double stranded d(AC)8 x d(GT) and single stranded d(AC)8 and d(GT)8 DNAs. The analysis of absorption revealed that the binding constants and the number of DNA binding sites for TMPyP3 were d(AC)8 < d(GT)8 < d(AC)8 x d(GT)8 = d(TTAGGG)4 < dTTAGGGTTAGAG(TTAGGG)2. We demonstrated for the first time that the binding constant of TMPyP3 with the non-quadruplex chain dTTAGGGTTAGAG(TTAGGG)2 (1.3 x 10(7) M(-1)) is approximately 3 times bigger than the binding constant with the quadruplex d(TTAGGG)4 (4.6 x 10(6) M(-1)). Binding of two TMPyP3 molecules to d(TTAGGG)4 led to a decrease of thermostability of the G-quadruplex (deltaT(m) = -8 degrees C). Circular dichroism spectra of TMPyP3:d(TTAGGG)4 complexes revealed a shift of DNA structure from the G-quadruplex to an irregular chain. We hypothesize that partial destabilization of the telomeric G-quadruplex by TMPyP3 might be a reason for relatively low potency of this ligand as a telomerase inhibitor, as well as its marginal cytotoxicity for cultured tumor cells.
authors.forename: Iu V
authors.initials: IuV
authors.lastname: Dutikova
authors.forename: O F
authors.initials: OF
authors.lastname: Borisova
authors.forename: A K
authors.initials: AK
authors.lastname: Shchelkina
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.forename: A A
authors.initials: AA
authors.lastname: Shtil'
authors.forename: D N
authors.initials: DN
authors.lastname: Kaliuzhnyĭ
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D009841:Oligonucleotides; D011166:Porphyrins; D019098:Telomerase