A contiguous stretch of methionine residues mediates the energy-dependent internalization mechanism of a cell-penetrating peptide.
Recently we characterized an unusual switch in the internalization mechanism of the monomeric and dimeric forms of the cell-penetrating peptide RDLWEMMMVSLACQY. Here, we observed both energy-dependent and energy-independent modes of peptide uptake by the target B-lymphocytes WI-L2-729HF2, suggesting that higher-order structure might modulate the action of this novel cell-penetrating peptide. In the present work, we propose a possible internalization mechanism for the dimeric peptide which involves an initial interaction with the cell membrane, followed by an energy-dependent internalization process which requires the contiguous Met(6-8) sequence.
Kim
Youngsoo
Y
The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
Lillo
Antonietta
A
Moss
Jason A
JA
Janda
Kim D
KD
D000595:Amino Acid Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D019281:Dimerization; D007700:Kinetics; D008715:Methionine; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*
D010455:Peptides; D008715:Methionine