Nα-Methylation of arginine: Implications for cell-penetrating peptides,Journal of Peptide Science

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Nα-Methylation of arginine: Implications for cell-penetrating peptides
Journal of Peptide Science ( IF 1.8 ) Pub Date : 2022-12-09 , DOI: 10.1002/psc.3468
Lindsey O Calabretta ₁ , Jinyi Yang ₁ , Ronald T Raines ₁

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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 N^α-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, N^α-methylation, can enhance the performance of cell-penetrating peptides.

中文翻译：

精氨酸的 Nα-甲基化：对细胞穿透肽的影响

细胞穿透肽领域主要是使用精氨酸残基的低聚物。在阴离子脂质存在下的辛醇-水分配是细胞穿透功效的有效代表。在这里，我们向 Ac-Arg-NH _{2添加一个、两个或三个}N -甲基，并检查对辛醇-水分配的影响。在不存在阴离子脂质的情况下，在辛醇层中无法检测到这些精氨酸衍生物。然而，在十二烷酸钠存在下，增加的N-甲基化与增加的辛醇分配相关，这预示着更高的细胞穿透能力。然后我们全面评估N ^α-甲基化的寡聚精氨酸肽，并在某些情况下观察到与规范的寡聚精氨酸肽相比它们的细胞渗透增加。这些发现表明，一种简单的修饰，N ^{α -}甲基化，可以增强细胞穿透肽的性能。

更新日期：2022-12-09

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