Evaluation of peptide secondary structure and intracellular uptake by introducing disubstituted amino acids into the amphipathic helical peptide C18AA
Amphipathic helical peptides are common among antimicrobial and cell membrane-permeable peptides, and amino acid substitutions within existing peptides have been an effective means of new peptide drug development. In the present study, we evaluated the effect of introducing a disubstituted amino aci...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715625000864 |
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| author | Takuma Kato Go Ofuka Ryota Kobayashi Akiko Asano Mitsunobu Doi |
| author_facet | Takuma Kato Go Ofuka Ryota Kobayashi Akiko Asano Mitsunobu Doi |
| author_sort | Takuma Kato |
| collection | DOAJ |
| description | Amphipathic helical peptides are common among antimicrobial and cell membrane-permeable peptides, and amino acid substitutions within existing peptides have been an effective means of new peptide drug development. In the present study, we evaluated the effect of introducing a disubstituted amino acid (dAA), which has a stabilizing effect on the helical structure of the amphiphilic peptide C18AA, on the secondary structure of C18AA and its intracellular uptake. Computational analysis was also used to calculate the changes in the thermal stability of the secondary structure caused by substitution to dAAs. The results revealed that peptides that assumed a stable helical structure in aqueous solution showed higher intracellular uptake. It was also revealed that the type and position of the substituted amino acids significantly affected the peptide's secondary structure and intracellular uptake. These results indicate that use of dAAs may be a promising approach to improving the intracellular uptake of existing amphipathic helical peptides. |
| format | Article |
| id | doaj-art-b05886520b454661b0f737e3d0c18dfa |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-b05886520b454661b0f737e3d0c18dfa2025-02-10T04:34:20ZengElsevierResults in Chemistry2211-71562025-03-0114102103Evaluation of peptide secondary structure and intracellular uptake by introducing disubstituted amino acids into the amphipathic helical peptide C18AATakuma Kato0Go Ofuka1Ryota Kobayashi2Akiko Asano3Mitsunobu Doi4Corresponding author.; Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki city, Osaka 569-1094, JapanFaculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki city, Osaka 569-1094, JapanFaculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki city, Osaka 569-1094, JapanFaculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki city, Osaka 569-1094, JapanFaculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki city, Osaka 569-1094, JapanAmphipathic helical peptides are common among antimicrobial and cell membrane-permeable peptides, and amino acid substitutions within existing peptides have been an effective means of new peptide drug development. In the present study, we evaluated the effect of introducing a disubstituted amino acid (dAA), which has a stabilizing effect on the helical structure of the amphiphilic peptide C18AA, on the secondary structure of C18AA and its intracellular uptake. Computational analysis was also used to calculate the changes in the thermal stability of the secondary structure caused by substitution to dAAs. The results revealed that peptides that assumed a stable helical structure in aqueous solution showed higher intracellular uptake. It was also revealed that the type and position of the substituted amino acids significantly affected the peptide's secondary structure and intracellular uptake. These results indicate that use of dAAs may be a promising approach to improving the intracellular uptake of existing amphipathic helical peptides.http://www.sciencedirect.com/science/article/pii/S2211715625000864Cell-penetrating peptideAmphipathic peptideNon-proteinogenic amino acidα,α-Disubstituted α-amino acidHelical structureMolecular operating environment (MOE) |
| spellingShingle | Takuma Kato Go Ofuka Ryota Kobayashi Akiko Asano Mitsunobu Doi Evaluation of peptide secondary structure and intracellular uptake by introducing disubstituted amino acids into the amphipathic helical peptide C18AA Results in Chemistry Cell-penetrating peptide Amphipathic peptide Non-proteinogenic amino acid α,α-Disubstituted α-amino acid Helical structure Molecular operating environment (MOE) |
| title | Evaluation of peptide secondary structure and intracellular uptake by introducing disubstituted amino acids into the amphipathic helical peptide C18AA |
| title_full | Evaluation of peptide secondary structure and intracellular uptake by introducing disubstituted amino acids into the amphipathic helical peptide C18AA |
| title_fullStr | Evaluation of peptide secondary structure and intracellular uptake by introducing disubstituted amino acids into the amphipathic helical peptide C18AA |
| title_full_unstemmed | Evaluation of peptide secondary structure and intracellular uptake by introducing disubstituted amino acids into the amphipathic helical peptide C18AA |
| title_short | Evaluation of peptide secondary structure and intracellular uptake by introducing disubstituted amino acids into the amphipathic helical peptide C18AA |
| title_sort | evaluation of peptide secondary structure and intracellular uptake by introducing disubstituted amino acids into the amphipathic helical peptide c18aa |
| topic | Cell-penetrating peptide Amphipathic peptide Non-proteinogenic amino acid α,α-Disubstituted α-amino acid Helical structure Molecular operating environment (MOE) |
| url | http://www.sciencedirect.com/science/article/pii/S2211715625000864 |
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