Interaction of a tricationic meso-substituted porphyrin with guanine-containing polyribonucleotides of various structures

Abstract

The interaction of a tricationic water-soluble meso-(N-methylpyridinium)-substituted porphyrin, TMPyP, derived from classic TMPyP4, with double-stranded poly(G) ⋅ poly(C) and four-stranded poly(G) polyribonucleotides has been studied in aqueous buffered solutions, pH 6.9, of low and near-physiological ionic strengths in a wide range of molar phosphate-to-dye ratios (P/D). To clarify the binding modes of TMPyP to biopolymers various spectroscopic techniques, including absorption and polarized fluorescence spectroscopy, Raman spectroscopy, and resonance light scattering, were used. As a result, two competitive binding modes were revealed. In solution of low ionic strength outside binding of the porphyrin to the polynucleotide backbone with self-stacking prevailed at low P/D ratios (P/D < 3.5). It manifested itself by the substantial quenching of porphyrin fluorescence. Also the formation of large-scale porphyrin aggregates was observed near the stoichiometric binding ratio. The spectral changes observed at P/D > 30 including emission enhancement were supposed to be caused by the embedding of partially stacked porphyrin J-dimers into the polymer groove. TMPyP binding to poly(G) induced a fluorescence increase 2.5 times as large as that observed for poly(G) ⋅ poly(C). In solution of near-physiological ionic strength the efficiency of external porphyrin binding was reduced substantially due to the competitive binding of Na ions with the polymer backbone. The spectroscopic characteristics of porphyrin bound to polynucleotides at different conditions were compared with those for free porphyrin.

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

“…However, TMPyP4 is not the best candidate in anticancer treatment, because it lacks selectivity and has high affinity for all the types of nucleic acids. Thus, different derivatives are now being explored for G4-nucleic acid binding, such as the one with propyl groups instead of methyl (TPrPyP4) (Wei et al 2009), and the tricationic porphyrin, tris(1-methyl-4-pyridinio)porphyrin, bearing the carboxyalkyl linker (TMPyP3+) (Ryazanova et al 2016). Nice examples of selective G4-targeting were reported for amphiphilic cationic porphyrin tri-meso(N-methyl-4-pyridyl), meso(N-tetradecyl-4-pyridyl)porphine (TMPyP4-C14) (Fig.…”

Spectroscopic study on binding of cationic Pheophorbide-ato antiparallel quadruplex Tel22

“…Substantial enhancement of porphyrin fluorescence at high P/D ratios was observed earlier upon binding of cationic and neutral Pheophorbide-a derivatives to quadruple poly(G) [9,33], as well as for complexes formed by TMPyP 3+ porphyrin with poly(G) [34] and Tel22 [31], porphyrin-phenazine conjugate metalized by Zn 2+ and Mn 3+ with poly(G) and Tel22 [35,31]. At the same time no enhancement of CatPheoa emission was observed upon its binding to double strand poly(G)poly(C) and poly(A)poly(U) [9], as well as to single strand poly(P) biopolymers [8].…”

Spectroscopic study of binding of a cationic Pheophorbide-a to an antiparallel quadruplex Tel22

“…Substantial enhancement of porphyrin fluorescence at high P/D ratios was observed earlier upon binding of cationic and neutral Pheophorbide-a derivatives to quadruple poly(G) [9,37], as well as for the complexes formed by TMPyP 3+ porphyrin with poly(G) [38] and Tel22 [35], porphyrin-imidazophenazine conjugate metalated by Zn 2+ and Mn 3+ with poly(G) and Tel22 [39,35]. At the same time, no enhancement of the CatPheo-a emission was observed upon its binding to double stranded poly(G)•poly(C) and poly(A)•poly(U) [9], as well as to single stranded poly(P) biopolymers [8].…”