title: Binding of new cationic porphyrin-tetrapeptide conjugates to nucleoprotein complexes.
abstract: 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. The binding modes were analyzed by fluorescent energy transfer, fluorescent life time and CD measurements. Intercalative binding is most feasible when tricationic ligands complex with DNA, especially when it is in close connection with protein capsid. It was found that larger ligand BMPCP-4P2 binds externally to encapsidated T7 DNA, and complex externally as well as by intercalation when the DNA accommodate to relaxed B-conformation. In the case of TMPCP and TMPCP-4P the intercalation is the predominant binding form both in nucleoprotein (NP) and preheated complexes. Further, melting experiments revealed that bound porphyrins do not influence the capsid stability or protein-DNA interactions, but efficiently stabilize the double helical structure of DNA without respect to binding form. A good correlation was found between porphyrin/base pair ration and DNA strand separation temperature.
authors.affiliation: Institute of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary. orosz.adam@med.semmelweis-univ.hu
authors.forename: Adám
authors.initials: A
authors.lastname: Orosz
authors.forename: Gábor
authors.initials: G
authors.lastname: Mező
authors.forename: Levente
authors.initials: L
authors.lastname: Herényi
authors.forename: Jan
authors.initials: J
authors.lastname: Habdas
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Majer
authors.forename: Beata
authors.initials: B
authors.lastname: Myśliwa-Kurdziel
authors.forename: Katalin
authors.initials: K
authors.lastname: Tóth
authors.forename: Gabriella
authors.initials: G
authors.lastname: Csík
mesh_terms: D017123:Bacteriophage T7 / Q000378:metabolism; D002412:Cations / Q000737:chemistry; D002942:Circular Dichroism; D004279:DNA, Viral / Q000737:chemistry / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D009698:Nucleoproteins / Q000737:chemistry* / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011166:Porphyrins / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D002412:Cations; D004279:DNA, Viral; D009698:Nucleoproteins; D009842:Oligopeptides; D011166:Porphyrins