Issue 19, 2013

Cellular uptake of octaarginine-conjugated tetraarylporphyrin included by per-O-methylated β-cyclodextrin

Abstract

This paper describes the synthesis, structural characterization and cellular uptake of a supramolecular 1 : 2 inclusion complex of meso-tetraphenylporphyrin having an octaarginine peptide chain (R8-TPP) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMe-β-CD). R8-TPP was synthesized by 2 approaches: (1) on-resin conjugation of the N-terminal of octaarginine with 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin, followed by cleavage from the resin, and (2) Michael addition reaction between 5-[4-(3-maleimidopropylamido)phenyl]-10,15,20-triphenylporphyrin and cysteine–octaarginine peptide (Cys–Arg8). The R8-TPP obtained from both the approaches formed stable inclusion complexes with TMe-β-CD by which non-substituted phenyl groups at the 10- and 20-positions were included to form trans-type 1 : 2 inclusion complexes. The complexation prevented the self-aggregation of R8-TPP, which resulted in the solubilisation of R8-TPP in aqueous media. A cellular uptake study using HeLa cells showed that R8-TPP complexed with TMe-β-CD in a serum-free medium was efficiently taken up by the cells and uniformly dispersed in the cytosol. In the serum-containing medium, the R8-TPP–TMe-β-CD complex dissociated, and the serum protein bound R8-TPP. The R8-TPP–protein complex was localized in the endosomes of the cells. The cytosol-dispersed R8-TPP showed a higher photo-induced cytotoxicity than its endosome-trapped counterpart.

Graphical abstract: Cellular uptake of octaarginine-conjugated tetraarylporphyrin included by per-O-methylated β-cyclodextrin

Supplementary files

Article information

Article type
Paper
Submitted
20 Nov 2012
Accepted
22 Mar 2013
First published
22 Mar 2013

Org. Biomol. Chem., 2013,11, 3203-3211

Cellular uptake of octaarginine-conjugated tetraarylporphyrin included by per-O-methylated β-cyclodextrin

H. Kitagishi, S. Hatada, T. Itakura, Y. Maki, Y. Maeda and K. Kano, Org. Biomol. Chem., 2013, 11, 3203 DOI: 10.1039/C3OB27248F

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