Oligo- and polypeptide conjugates of cationic porphyrins: binding, cellular uptake, and cellular localization

Ádám Orosz, Szilvai Bősze, G. Mező, Ildikó Szabó, Levente Herényi, G. Csík

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Recently, we have characterized the DNA and nucleoprotein (NP) binding of bis(4-N-methylpyridyl)-15,20-di(4-carboxyphenyl)porphyrin (BMPCP) and meso-tri(4-N-methylpyridyl)-mono(4-carboxyphenyl)porphyrin (TMPCP) and their tetrapeptide conjugates (BMPCP-4P2 and TMPCP-4P, respectively). In this work, we investigated the interaction of TMPCP conjugated to the tetrapeptide branches of branched chain polymeric polypeptide with poly-l-lysine backbone (AK) with DNA or NP using spectroscopic methods. Analysis of absorption spectra revealed the external binding but no intercalation of TMPCP-AK to DNA. There was no evidence for the interaction between TMPCP-AK and encapsidated DNA. Furthermore, we examined the cellular uptake of BMPCP and TMPCP and their tetra- or polypeptide conjugates by flow cytometry and analyzed how charge, size, and structure of the compounds affect their incorporation. In comparison, liposomal association constants of these derivatives were determined. BMPCP-4P2 accumulated the most, and porphyrins with two positive charges (BMPCP and BMPCP-4P2) showed better accumulation than the tri-cationic TMPCP or TMPCP-4P. Cellular uptake of polycationic TMPCP-AK was significantly lower than that of the free or tetrapeptide conjugated derivatives. The subcellular localization of all the five compounds was investigated in co-localization studies by confocal microscopy with special attention to their nuclear localization. Neither free nor conjugated BMPCP or TMPCP was co-localized with nuclear marker. Instead, these derivatives showed co-localization with lysosomal and mitochondrial fluorescent probes. TMPCP-AK conjugate had different localization patterns appearing mainly in mitochondria and cytoplasmic vesicles. Our results may contribute to the further design of DNA-targeting porphyrin-based constructs.

Original languageEnglish
Pages (from-to)1263-1276
Number of pages14
JournalAmino Acids
Volume49
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

Fingerprint

Oligopeptides
Porphyrins
Peptides
DNA
Nucleoproteins
Derivatives
Cytoplasmic Vesicles
Mitochondria
Flow cytometry
Confocal microscopy
Intercalation
Fluorescent Dyes
Confocal Microscopy
Lysine
Absorption spectra
Spectrum Analysis
Flow Cytometry
Association reactions

Keywords

  • Cationic porphyrin
  • Cellular uptake
  • DNA binding
  • Intracellular localization
  • Lipid association constant
  • Peptide conjugate

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Oligo- and polypeptide conjugates of cationic porphyrins : binding, cellular uptake, and cellular localization. / Orosz, Ádám; Bősze, Szilvai; Mező, G.; Szabó, Ildikó; Herényi, Levente; Csík, G.

In: Amino Acids, Vol. 49, No. 7, 01.07.2017, p. 1263-1276.

Research output: Contribution to journalArticle

Orosz, Ádám ; Bősze, Szilvai ; Mező, G. ; Szabó, Ildikó ; Herényi, Levente ; Csík, G. / Oligo- and polypeptide conjugates of cationic porphyrins : binding, cellular uptake, and cellular localization. In: Amino Acids. 2017 ; Vol. 49, No. 7. pp. 1263-1276.
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AU - Herényi, Levente

AU - Csík, G.

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