Drug Self-Assembly on DNA: Sequence Effects withtrans-bis-(4-N-methylpyridiniumyl)diphenyl Porphyrin and Hoechst 33258

Abstract

Self assembly in biological systems is increasingly being recognised as an important phenomenon. We have examined two model systems: the cationic meso-substituted free base porphyrin derivative frans-bis-(4-N-methylpyridiniumyl)diphenyl porphyrin (t-H(2)P) and Hoechst 33258 (Hoechst) both of which were known to assemble on DNA. t-H(2)P self-assembles in solution under appropriate conditions, whereas Hoechst does not. By varying ionic strength and ligand: DNA mixing ratios, these features together with their different steric constraints have led to quite different DNA binding behaviour. Hoechst on poly[d(A-T)](2) stacks across the major groove, probably after filling its well established monomeric minor groove binding mode. By way of contrast the Hoechst/poly[d(G-C)](2) self-assembled aggregates involve partially intercalated molecules stacking in the major groove. The binding mode adopted by t-H(2)P with poly[d(A-T)](2) and poly[d(G-C)](2) appears to be kinetically controlled and to be determined by the pre-existence of monomer binding and/or ligand stacks in solution. With poly[d(A-T)](2) the modes adopted both involve displacing the DNA bases to be more parallel than perpendicular to the helix axis. One is probably based on porphyrin intercalation and the other on minor groove binding. Resonance light scattering, linear dichroism, circular dichroism, normal absorption and fluorescence spectroscopies have been used to characterise the self-assembly in these systems.

Binding of meso-Tetrakis(N-methylpyridinium-4-yl)porphyrin to AT Oligomers: Effect of Chain Length and the Location of the Porphyrin Stacking

“…In other words, R ¼ 1 indicates 1 porphyrin per 12 basepairs and base triplets for the 12mer duplex and triplex, respectively, and 1 porphyrin per 6 basepairs for 6mers. The appearance of spectra for the porphyrin-DNA system is affected by the order of mixing (Ismail et al, 2000). Therefore, in this study, aliquots of concentrated TMPyP (typically ;200 mM) were always added last to the DNA solution.…”

“…It has been known that some porphyrins stack by themselves in aqueous solution (Ismail et al, 2000;Pasternack et al, 2001) and produce hypochromism in the Soret absorption region. The extent of the self-stacking depends on the salt and porphyrin concentration.…”

“…The extensively stacked porphyrin is related to the inducing of the DNA aggregation. The porphyrins that have been known to stack outside of the DNA include meso-tetrakis(p-tri-N-methylpyridiniumyl)porphyrin Banville et al, 1986;LeDoan et al, 1987), meso-tetrakis[4-[3-(trimethylammonio)prophyloxy]phenyl]porphyrin (Mukundan et al, 1994(Mukundan et al, , 1995, trans-bis(N-methylpyridinium-4-yl)diphenyl porphyrin (Pasternack et al, 1998;Ismail et al, 2000), and some copper(II)porphyrins (Pasternack et al, 2001). Despite the extensive studies on the outside-stacking of porphyrin to DNA, the exact location where the stacking occurs still remains undetermined.…”

Thermodynamic analysis of DNA complexes with methylene blue, ethidium bromide and Hoechst 33258

“…Nowadays the ligands noncovalently binding with DNA are divided into two classes -intercalators and groove binding compounds [8][9][10][11][12][13][14][15][16]. However, the results of theoretical and experimental investigations show that depending on the external medium conditions several ligands may bind to double-stranded (ds-) or single-stranded (ss-) DNA in more than one mode (multimodal ligands) [17][18][19][20][21][22][23][24][25]. From this point of view methylene blue (MB, Fig.…”

CD and DSC Investigation of Individual and Complex Influence of Meso-Tetra(4-Oxiethylpyridil) Porphyrin (TOEPyP4) and Its Zn-Complex on DNA

“…It was shown [7] that porphyrin plane molecules TMPyP intercalate between the base pairs of DNA double helix and they bind only to 5'CG3' areas, and not to other sequences. Outside binding modes were studied in works [6][7][8][9][10][11]. It was also shown that these binding modes were formed mainly by porphyrins having axial ligands, which were absorbed on AT rich areas located in minor and major grooves, as well as double helix surface of DNA [12].…”