Products Cited in Publications Worldwide Nα-Methylation of arginine: Implications for cell-penetrating peptides

Nα-Methylation of arginine: Implications for cell-penetrating peptides

Calabretta, Lindsey O.; Yang, Jinyi; Raines, Ronald T.

DOI: PMID:

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-Me 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.

Keywords

guanidino group ; octanol-water partitioning ; peptoid ; topological polar surface area

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