Interaction of DNA with a porphyrin ligand: evidence for intercalation

Fiel, Robert J.; Howard, J. C.; Mark, E.H.; Gupta, Nisha

doi:10.1093/nar/6.9.3093

Cited by 349 publications

(302 citation statements)

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“…The binding of cationic porphyrin derivatives to nucleic acids has been the subject of extensive research since Fiel and colleagues discovered that these compounds can form various complexes with DNA [8]. It has been shown that the binding can be either intercalative or external, in the minor groove (in some special cases with self-stacking), depending on the charge distribution of the porphyrin, presence and the type of the central metal ion in porphyrin and on the peripheral substituents [9].…”

Section: Introductionmentioning

confidence: 99%

Syntheses and DNA binding of new cationic porphyrin–tetrapeptide conjugates

Mező

Herényi

Habdas

et al. 2011

Biophysical Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractRecently 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. Tetra-peptides were linked to the tri-cationic meso-tri A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT Graphical AbstractResearch Highlights We synthesized two new porphyrin-tetrapeptide conjugates. DNA binding of porphyrin conjugates was studied with spectroscopic methods. Peptide conjugates of cationic porphyrins bind to DNA by two distinct binding modes. Binding modes can be identified as intercalation and external binding.

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Section: Introductionmentioning

confidence: 99%

Syntheses and DNA binding of new cationic porphyrin–tetrapeptide conjugates

Mező

Herényi

Habdas

et al. 2011

Biophysical Chemistry

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“…From this point of view, cationic meso-tetrakis(4-N-methylpyridiniumyl)porphine (TMPyP) has been carefully studied and noted for its bifunctionality: i) the tight interaction with DNA through the three types of binding mode including intercalation, outside binding in the groove, and outside binding with self-stacking along the DNA surface, 6,7) and ii) the marked photochemical nuclease activity. [8][9][10] Such a positively charged photosensitizer 11,12) would also be useful in the photodynamic therapy of cancer. 13,14) Some hybrid molecules composed of a non-charged porphyrin and acridines have been synthesized as a functional BLM model.…”

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confidence: 99%

Efficient Photocleavage of DNA by Cationic Porphyrin. Acridine Hybrids with the Effective Length of Diamino Alkyl Linkage.

Ishikawa

Yamashita

Uno

2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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The development of compounds which modify nucleic acid structure is a current research area and can make a significant contribution to anti-tumor and -viral chemotherapy.1,2) For example, drugs like bleomycin (BLM) [3][4][5] capable of binding to and cleaving nucleic acids are expected to suppress the proliferation of malignant cells by blocking the flow of genetic information. From this point of view, cationic meso-tetrakis(4-N-methylpyridiniumyl)porphine (TMPyP) has been carefully studied and noted for its bifunctionality: i) the tight interaction with DNA through the three types of binding mode including intercalation, outside binding in the groove, and outside binding with self-stacking along the DNA surface, 6,7) and ii) the marked photochemical nuclease activity.8-10) Such a positively charged photosensitizer 11,12) would also be useful in the photodynamic therapy of cancer. 13,14) Some hybrid molecules composed of a non-charged porphyrin and acridines have been synthesized as a functional BLM model. [15][16][17] Acridine is known as an intercalator, 18,19) and hence the metal complexes of the hybrids bind to DNA via the acridine moiety, and then cause strand breaks by generating reactive oxygen species in the presence of reducing or oxidizing agents. To achieve higher and more efficient chemical modification of negatively charged DNA, we have for the first time synthesized positively charged porphyrin-acridine hybrids, 1-4, which are linked with various lengths of a diamino alkyl chain. In this paper we report their photo-nuclease activity and interaction with DNA. Our data show that they exhibit more enhanced photo-induced nuclease activity than TMPyP, and suggest that acridine and porphyrin moiety in the hybrids interact with DNA by the intercalative and outside groove binding, respectively. Results and DiscussionSynthesis of the Cationic Porphyrin-Acridine HybridsThe synthetic procedures for the positively charged porphyrin-acridine hybrids 1-4 are illustrated in Chart 1. One equivalent of terephthalaldehydic acid methyl ester, 3 eq of pyridine-4-aldehyde, and 4 eq of pyrrole were reacted in propionic acid for 1.5 h. The resultant mixture including six porphyrin isomers was separated on silica gel. The fifth eluted isomer, 5-(4-methoxycarbonylphenyl)-10,15,20-tris(4-pyridyl)-porphine, 9, obtained in 5.9% yield was then hydrolyzed with lithium hydroxide to give 5-(4-carboxyphenyl)-10,15,20-tris(4-pyridyl)porphine, 10, almost quantitatively. Condensation of 1 eq of 10 with 5-7 eq of acridine-diaminoalkane derivatives, 20) 5-8, using 5-7 eq of carbonyldiimidazole (CDI) in an absolute 50/50 (v/v) DMF-DMSO solution afforded corresponding porphyrin-acridine hybrids, 11-14, in 22-46% yield. The products were then methylated with excess methyl iodide in DMF for 3 h to give the final products, 1-4, quantitatively. Characterization of the compounds was accomplished using 1 H-NMR spectroscopy, matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and elemental analysis.Photo...

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“…The study of porphyrins DNA binding capacity is extensive [367][368][369] , especially in the area of cationic porphyrins since the discovery of their ability to form several different complexes with DNA [370] . In recent years this research has expanded to incorporate bioactive functionalities for targeting.…”

Section: Formula 19mentioning

confidence: 99%

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

Moylan¹,

Scanlan²,

Senge

2015

CMC

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Abstract:This review presents an in-depth overview of the modification of porphyrins with bioconjugates and their applications in medicine today. Porphyrin bioconjugates ranging from nucleotides to steroids are under active scrutiny. However, carbohydrates have been at the forefront of such research in recent years and offer significant potential. This is attributed to their own selectivity to lectins on the surface of cancer cells and their influence on the amphiphilicity of the porphyrin macrocycle. These characteristics and the tendency of porphyrin photosensitizers to accumulate in tumor tissues make glycoporphyrins promising candidates for use as photosensitizers. Thus, a detailed overview of the synthesis and biological evaluation of glycoporphyrins is given with a particular focus on their applications in photodynamic therapy and their future prospects as drug candidates have been reported.

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Interaction of DNA with a porphyrin ligand: evidence for intercalation

Cited by 349 publications

References 19 publications

Syntheses and DNA binding of new cationic porphyrin–tetrapeptide conjugates

Syntheses and DNA binding of new cationic porphyrin–tetrapeptide conjugates

Efficient Photocleavage of DNA by Cationic Porphyrin. Acridine Hybrids with the Effective Length of Diamino Alkyl Linkage.

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

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