RRC ID 44386
著者 Kitagishi H, Hatada S, Itakura T, Maki Y, Maeda Y, Kano K.
タイトル Cellular uptake of octaarginine-conjugated tetraarylporphyrin included by per-O-methylated β-cyclodextrin.
ジャーナル Org Biomol Chem
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.
巻・号 11(19)
ページ 3203-11
公開日 2013-5-21
DOI 10.1039/c3ob27248f
PMID 23584796
MeSH Cell Death / drug effects Cell Survival / drug effects Dose-Response Relationship, Drug HeLa Cells Humans Methylation Molecular Structure Oligopeptides / chemical synthesis Oligopeptides / chemistry Oligopeptides / pharmacology* Porphyrins / chemical synthesis Porphyrins / chemistry Porphyrins / pharmacology* Structure-Activity Relationship beta-Cyclodextrins / chemistry beta-Cyclodextrins / pharmacology*
IF 3.412
引用数 18
WOS 分野 CHEMISTRY, ORGANIC
リソース情報
ヒト・動物細胞 HeLa