Amino Acids

, Volume 49, Issue 7, pp 1263–1276 | Cite as

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

  • Ádám Orosz
  • Szilvai Bősze
  • Gábor Mező
  • Ildikó Szabó
  • Levente Herényi
  • Gabriella CsíkEmail author
Original Article


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.


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



This work was supported by research grant Országos Tudományos Kutatási Alapprogramok (OTKA) K104045 and K104275.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag Wien 2017

Authors and Affiliations

  1. 1.Institute of Biophysics and Radiation BiologySemmelweis UniversityBudapestHungary
  2. 2.Research Group of Peptide Chemistry, Hungarian Academy of SciencesEötvös Loránd UniversityBudapestHungary

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