Title :

A novel amphipathic cell-penetrating peptide based on the N-terminal glycosaminoglycan binding region of human apolipoprotein E

Author(s) :

Ohgita, Takashi [Auteur]
Takechi-Haraya, Yuki [Auteur]
Nadai, Ryo [Auteur]
Kotani, Mana [Auteur]
Tamura, Yuki [Auteur]
Nishikiori, Karin [Auteur]
Nishitsuji, Kazuchika [Auteur]
Uchimura, Kenji [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Hasegawa, Koki [Auteur]
Sakai-Kato, Kumiko [Auteur]
Akaji, Kenichi [Auteur]
Saito, Hiroyuki [Auteur]

Journal title :

Biochimica et Biophysica Acta (BBA) - Biomembranes

Abbreviated title :

Biochimica et Biophysica Acta (BBA) - Biomembranes

Volume number :

1861

Pages :

541-549

Publisher :

Elsevier BV

Publication date :

2019-03-01

ISSN :

0005-2736

English keyword(s) :

Arginine-rich peptide
Amphipathicity
Glycosaminoglycan
Lipid membrane
Cell membrane penetration

HAL domain(s) :

Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique

English abstract : [en]

In the direct cell membrane penetration, arginine-rich cell-penetrating peptides are thought to penetrate intocells across the hydrophobic lipid membranes. To investigate the effect of the amphipathic property of arginine-rich ...
Show more >In the direct cell membrane penetration, arginine-rich cell-penetrating peptides are thought to penetrate intocells across the hydrophobic lipid membranes. To investigate the effect of the amphipathic property of arginine-rich peptide on the cell-penetrating ability, we designed a novel amphipathic cell-penetrating peptide, A2-17,and its derivative, A2-17KR, in which all lysine residues are substituted with arginine residues, based on theglycosaminoglycan binding region in the N-terminalα-helix bundle of human apolipoprotein E. Isothermal ti-tration calorimetry showed that A2-17 variants have a strong ability to bind to heparin with high affinity.Circular dichroism and tryptophanfluorescence measurements demonstrated that A2-17 variants bind to lipidvesicles with a structural change from random coil to amphipathicα-helix, being inserted into the hydrophobicmembrane interiors. Flow cytometric analysis and confocal laser scanning microscopy demonstrated the greatcell penetration efficiency of A2-17 variants into CHO-K1 cells when incubated at low peptide concentrations(2μM or less), suggesting that the increased amphipathicity withα-helix formation enhances the cell membranepenetration ability of arginine-rich peptides. Interestingly, A2-17KR exhibited lower efficiency of cell membranepenetration compared to A2-17 despite of their similar binding affinity to lipid membranes. Since high peptideconcentrations (typically > 10μM) are usually prerequisite for efficient cell penetration of arginine-rich pep-tides, A2-17 is a unique amphipathic cell-penetrating peptide that exhibits an efficient cell penetration abilityeven at low peptide concentrations.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Diversité structurale des héparanes sulfates et régulation de la réponse inflammatoire

Submission date :

2020-12-14T10:20:59Z
2020-12-16T16:46:19Z