On the mechanism of eukaryotic cell penetration by α- and β-oligoarginines--targeting infected erythrocytes.
Fluorescein-labeled α- and β-octaarginine amides were synthesized. The route, by which these oligoarginine (OA) derivatives enter cells (hepatocytes, fibroblasts, macrophages), was investigated by confocal fluorescence microscopy. Comparisons (by co-localization experiments) with compounds of known penetration modes revealed that the β-octaarginine amide also uses multiple pathways to enter cells. There was no difference between the α- and the β-OAs. Like other cell-penetrating peptides (CPPs), the β-octaarginine eventually winds up in the nucleoli of the cell nuclei (cf. Chem. Biodiversity, 2004, 1, 65). Surprisingly, there was no entry of α- or β-OA into intact and healthy human erythrocytes (which do not possess a nucleus). Blood cells infected by Plasmodium falciparum (malaria parasite) were, however, entered readily, and the OAs went all the way through a couple of membranes into the parasite. The potential of these results for delivering specific antimalarial drugs directly into the parasite is discussed.
Max-Planck-Institute of Colloids and Interfaces, Department of Biomolecular Systems, Free University Berlin, Institute of Chemistry and Biochemistry, Arnimallee 22, Berlin. faustin.kamena@mpikg.mpg.de
Faustin
F
Kamena
Bopanna
B
Monnanda
Danielle
D
Makou
Stefania
S
Capone
Krystyna
K
Patora-Komisarska
Dieter
D
Seebach
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D007536:Isomerism; D051379:Mice; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats
D000962:Antimalarials; D057846:Cell-Penetrating Peptides; D009842:Oligopeptides; C448619:octaarginine