Nα-Methylation of arginine: Implications for cell-penetrating peptides
Name
Journal of Peptide Science - 2022 - Calabretta - N ‐Methylation of arginine Implications for cell‐penetrating peptides.pdf
Description
Published version
Size
865.63 KB
Format
Adobe PDF
Checksum (MD5)
d0806fcfdb23353d5b006bd4aae2a50d
Author(s)
Calabretta, Lindsey O
Yang, Jinyi
Raines, Ronald T
Date Issued
December 9, 2022
Journal
Journal of Peptide Science
Publisher
Wiley
Citation
Calabretta, Lindsey O, Yang, Jinyi and Raines, Ronald T. 2022. "Nα-Methylation of arginine: Implications for cell-penetrating peptides." Journal of Peptide Science.
Version
Final published version
Abstract
The field of cell-penetrating peptides is dominated by the use of oligomers of arginine residues. Octanol-water partitioning in the presence of an anionic lipid is a validated proxy for cell-penetrative efficacy. Here, we add one, two, or three N-methyl groups to Ac-Arg-NH2 and examine the effects on octanol-water partitioning. In the absence of an anionic lipid, none of these arginine derivatives can be detected in the octanol layer. In the presence of sodium dodecanoate, however, increasing N-methylation correlates with increasing partitioning into octanol, which is predictive of higher cell-penetrative ability. We then evaluated fully Nα -methylated oligoarginine peptides and observed an increase in their cellular penetration compared with canonical oligoarginine peptides in some contexts. These findings indicate that a simple modification, Nα -methylation, can enhance the performance of cell-penetrating peptides.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1002/psc.3468
