NDA@SZTAKI

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

Orosz, Ádåm

Bősze, Szilvia

Mező, Gábor

SzabĂł, IldikĂł

HerĂŠnyi, Levente

Csik, Gabriella

Springer

2017-04-27

QD04 Organic chemistry / szerves kĂŠmia

QH3020 Biophysics / biofizika

Recently, we have characterized the DNA and
nucleoprotein (NP) binding of bis(4-N-methylpyridyl)-
15,20-di(4-carboxyphenyl)porphyrin (BMPCP) and mesotri(
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. TMPCPAK
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.

magyar

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/74291/1/Orosz_Manuscriptcorr_no_ny.pdf

Orosz, Ádám and Bősze, Szilvia and Mező, Gábor and Szabó, Ildikó and Herényi, Levente and Csik, Gabriella (2017) Oligo‑ and polypeptide conjugates of cationic porphyrins: binding, cellular uptake, and cellular localization. Amino Acids, 49. pp. 1263-1276. ISSN 1438-2199

http://real.mtak.hu/74291/

https://doi.org/10.1007/s00726-017-2428-z

doi: 10.1007/s00726-017-2428-z