Nα-Methylation of arginine: Implications for cell-penetrating peptides
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 o...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023
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| Online Access: | https://hdl.handle.net/1721.1/148050 |
| _version_ | 1811094895152070656 |
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| author | Calabretta, Lindsey O Yang, Jinyi Raines, Ronald T |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Calabretta, Lindsey O Yang, Jinyi Raines, Ronald T |
| author_sort | Calabretta, Lindsey O |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:06:53Z |
| format | Article |
| id | mit-1721.1/148050 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:06:53Z |
| publishDate | 2023 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1480502023-02-15T03:03:24Z Nα-Methylation of arginine: Implications for cell-penetrating peptides Calabretta, Lindsey O Yang, Jinyi Raines, Ronald T Massachusetts Institute of Technology. Department of Chemistry 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. 2023-02-14T17:24:19Z 2023-02-14T17:24:19Z 2022-12-09 2023-02-14T17:17:57Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/148050 Calabretta, Lindsey O, Yang, Jinyi and Raines, Ronald T. 2022. "Nα-Methylation of arginine: Implications for cell-penetrating peptides." Journal of Peptide Science. en 10.1002/psc.3468 Journal of Peptide Science Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Wiley Wiley |
| spellingShingle | Calabretta, Lindsey O Yang, Jinyi Raines, Ronald T Nα-Methylation of arginine: Implications for cell-penetrating peptides |
| title | Nα-Methylation of arginine: Implications for cell-penetrating peptides |
| title_full | Nα-Methylation of arginine: Implications for cell-penetrating peptides |
| title_fullStr | Nα-Methylation of arginine: Implications for cell-penetrating peptides |
| title_full_unstemmed | Nα-Methylation of arginine: Implications for cell-penetrating peptides |
| title_short | Nα-Methylation of arginine: Implications for cell-penetrating peptides |
| title_sort | nα methylation of arginine implications for cell penetrating peptides |
| url | https://hdl.handle.net/1721.1/148050 |
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