[Complexes of antiparallel telomeric G-quadruplex d(TTAGGG)4 with carboxymethyl tetracationic porphyrins].

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

[Role of the medium acidity in the complexes formation of pyropheophorbide a with albumin and lipoproteins].

The spectral characteristics of the photosensitizer pyropheophorbide a (PPP) complexes with its carriers, that is, serum albumin and low density lipoproteins, were investigated in aqueous solutions at pH 7.4 and 5.0. The acidic pH had no effect on the quantitative parameters of PPP binding to lipoproteins but reduces its affinity for albumin. Differential role of acidification in the binding of PPP to biomacromolecules should be considered in the design of PPP-based drugs given that pH is frequently lowered in the sites of the disease.