title: Syntheses and DNA binding of new cationic porphyrin-tetrapeptide conjugates.
abstract: 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. Tetra-peptides were linked to the tri-cationic meso-tri(4-N-methylpyridyl)-mono-(4-carboxyphenyl)porphyrin and bi-cationic meso-5,10-bis(4-N-methylpyridyl)-15,20-di-(4-carboxyphenyl)porphyrin. DNA binding of porphyrin derivatives, and their peptide conjugates was investigated with comprehensive spectroscopic methods. Titration of porphyrin conjugates with DNA showed changes in Soret bands with bathocromic shifts and hypochromicities. Decomposition of absorption spectra suggested the formation of two populations of bound porphyrins. Evidence provided by the decomposition of absorption spectra, fluorescence decay components, fluorescence energy transfer and induced CD signals reveals that peptide conjugates of di- and tricationic porphyrins bind to DNA by two distinct binding modes which can be identified as intercalation and external binding. Tri-cationic structure and elimination of negative charges in the peptide conjugates are preferable for the binding. Our findings provide essential information for the design of DNA-targeted porphyrin-peptide conjugates.
authors.affiliation: Research Group of Peptide Chemistry, Hungarian Academy of Science, Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest 1117, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Mezo
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: D001665:Binding Sites; D002412:Cations / Q000737:chemistry; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D004735:Energy Transfer; D010455:Peptides / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*
chemical_list: D002412:Cations; D010455:Peptides; D011166:Porphyrins; D004247:DNA