論文

査読有り 国際誌
2020年6月15日

Enhancing the activity of membrane remodeling epsin-peptide by trimerization.

Bioorganic & medicinal chemistry letters
  • Wei-Yuan Hsu
  • ,
  • Toshihiro Masuda
  • ,
  • Sergii Afonin
  • ,
  • Takayuki Sakai
  • ,
  • Jan Vincent V Arafiles
  • ,
  • Kenichi Kawano
  • ,
  • Hisaaki Hirose
  • ,
  • Miki Imanishi
  • ,
  • Anne S Ulrich
  • ,
  • Shiroh Futaki

30
12
開始ページ
127190
終了ページ
127190
記述言語
英語
掲載種別
DOI
10.1016/j.bmcl.2020.127190

Modulating the structural dynamics of biomembranes by inducing bilayer curvature and lipid packing defects has been highlighted as a practical tool to modify membrane-dependent cellular processes. Previously, we have reported on an amphipathic helical peptide derived from the N-terminal segment (residues 1-18, EpN18) of epsin-1, which can promote membrane remodeling including lipid packing defects in cell membranes. However, a high concentration is required to exhibit a pronounced effect. In this study, we demonstrate a significant increase in the membrane-remodeling effect of EpN18 by constructing a branched EpN18 homotrimer. Both monomer and trimer could enhance cell internalization of octaarginine (R8), a cell-penetrating peptide. The EpN18 trimer, however, promoted the uptake of R8 at an 80-fold lower concentration than the monomer. Analysis of the generalized polarization of a polarity-sensitive dye (di-4-ANEPPDHQ) revealed a higher efficacy of trimeric EpN18 in loosening the lipid packing in the cell membrane. Circular dichroism measurements in the presence of lipid vesicles showed that the EpN18 trimer has a higher α-helix content compared with the monomer. The stronger ability of the EpN18 trimer to impede negative bilayer curvature is also corroborated by solid-state 31P NMR spectroscopy. Hence, trimerizing peptides can be considered a promising approach for an exponential enhancement of their membrane-remodeling performance.

リンク情報
DOI
https://doi.org/10.1016/j.bmcl.2020.127190
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32317210

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