Anionic fullerenes, calixarenes, coronenes, and pyrenes as activators of oligo/polyarginines in model membranes and live cells.
We report that the efflux of 5(6)-carboxyfluorescein anions from neutral egg yolk phosphatidylcholine vesicles is mediated by oligo/polyarginines only in the presence of activating amphiphilic anions. Screening of anion activators reveals best synergism for amphiphilic carboxylates (fullerene > calix[4]arene approximately coronene > pyrene > calix[6]arene > alkyl), whereas amphiphilic sulfates show less satisfactory activation despite often lower effective concentrations. The analogous alcohols and one calix[4]arene diphosphate were inactive. These results are discussed in the context of a tentative anion carrier mechanism, where interactions with bilayer (interface-directed translocation) and carrier (arene-templated carboxylate-guanidinium pairing) contribute to activator efficiencies. Applied to HeLa cells, pyrenebutyrate is shown to significantly increase the uptake of a fluorescently labeled octaarginine in a concentration-dependent manner.
Perret
Florent
F
Department of Organic Chemistry, University of Geneva, Geneva, Switzerland, Institute for Chemical Research, Kyoto University and PRESTO, JST, Kyoto, Japan.
Nishihara
Masamichi
M
Takeuchi
Toshihide
T
Futaki
Shiroh
S
Lazar
Adina N
AN
Coleman
Anthony W
AW
Sakai
Naomi
N
Matile
Stefan
S
D000838:Anions; D047250:Calixarenes / Q000737:chemistry / Q000493:pharmacokinetics*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D037741:Fullerenes / Q000737:chemistry / Q000493:pharmacokinetics*; D006367:HeLa Cells; D006801:Humans; D008567:Membranes, Artificial; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics*; D010715:Phosphatidylglycerols / Q000737:chemistry; D011083:Polycyclic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D011721:Pyrenes / Q000737:chemistry / Q000493:pharmacokinetics*
D000838:Anions; D004337:Drug Carriers; D037741:Fullerenes; D008567:Membranes, Artificial; D010455:Peptides; D010715:Phosphatidylglycerols; D011083:Polycyclic Compounds; D011721:Pyrenes; D047250:Calixarenes; C015462:polyarginine; C012256:coronene