Lowering the overall charge on TMPyP4 improves its selectivity for G-quadruplex DNA.

Ligands that stabilize non-canonical DNA structures called G-quadruplexes (GQs) might have applications in medicine as anti-cancer agents, due to the involvement of GQ DNA in a variety of cancer-related biological processes. Five derivatives of 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4), where a N-methylpyridyl group was replaced with phenyl (4P3), 4-aminophenyl (PN3M), 4-phenylamidoproline (PL3M), or 4-carboxyphenyl (PC3M and P2C2M) were investigated for their interactions with human telomeric DNA (Tel22) using fluorescence resonance energy transfer (FRET) assay, and UV-visible and circular dichroism spectroscopies in K buffer. The molecules are cationic or zwitterionic with an overall charge of 3+ (4P3, PN3M, and PL3M), 2+ (PC3M) or neutral (P2C2M).

Binding of new cationic porphyrin-tetrapeptide conjugates to nucleoprotein complexes.

Ongoing research on DNA binding of cationic porphyrin derivatives and their conjugates is a subject of growing interest because of their possible DNA binding and demonstrated biological properties. In this study nucleoprotein binding of tri-cationic meso-tri(4-N-methylpyridyl)-mono-(4-carboxyphenyl)porphyrin (TMPCP) and tetrapeptides conjugated TMPCP (TMPCP-4P) and bi-cationic meso-5,10-bis(4-N-methylpyridyl)-15,20-di-(4-carboxyphenyl)porphyrin (BMPCP-4P2) was investigated with comprehensive spectroscopic methods. The key observation is that tetrapeptide-conjugates of cationic porphyrins with two or three positive charges bind to encapsidated DNA in T7 phage nucleoprotein complex.

Syntheses and DNA binding of new cationic porphyrin-tetrapeptide conjugates.

Recently cationic porphyrin-peptide conjugates were synthesized to enhance the cellular uptake of porphyrins or deliver the peptide moiety to the close vicinity of nucleic acids. DNA binding of such compounds was not systematically studied yet. We synthesized two new porphyrin-tetrapeptide conjugates which can be considered as a typical monomer unit corresponding to the branches of porphyrin-polymeric branched chain polypeptide conjugates.

Synthesis of 5-(4'-carboxyphenyl)-10,15,20-tris-(4 pyridyl)-porphyrin and its peptidyl phosphonate derivatives.

The synthesis and characterization of three new 4-pyridyl porphyrin-peptidyl-phosphonate compounds, containing a diphenyl 3-pyridylmethyl-phosphonate moiety, is described in this article. Nitrogen atoms in the pyridine rings of the obtained compounds were alkylated using methyl iodide, to give additional three, water soluble derivatives of these peptidyl-porphyrin conjugates. All the synthesized compounds could serve as potential photosensitizers for the photodynamic therapy (PDT) method of tumor therapy and displayed activity as inhibitors of aminopeptidase N.

Photodynamic effects of two water soluble porphyrins evaluated on human malignant melanoma cells in vitro.

Two water soluble porphyrins: meso-tetra-4-N-methylpyridyl-porphyrin iodide (P1) and 5,10-di-(4-acetamidophenyl)-15,20-di-(4-N-methylpyridyl) porphyrin (P2) were synthesised and evaluated in respect to their photochemical and photophysical properties as well as biological activity. Cytotoxic and phototoxic effects were evaluated in human malignant melanoma Me45 line using clonogenic assay, cytological study of micronuclei, apoptosis and necrosis frequency and inhibition of growth of megacolonies. Both porphyrins were characterised by high UV and low visible light absorptions.