Peptide Stapling Applied to Antimicrobial Peptides
Abstract
:1. Introduction
2. Antimicrobial Peptide Stapling
2.1. All-Hydrocarbon Stapling
Peptide | Origin | Stapling Style | Amino Acid Substitution | Antimicrobial Activity | Cytotoxicity | Helix Content | Proteolysis Susceptibility | References |
---|---|---|---|---|---|---|---|---|
P9 | CXCL10 chemokine | All-hydrocarbon (i, i + 4); position 8 and 12 | No | Improved | Increased | Increased | NA | [48] |
MPIS | Polybia-MPI | All-hydrocarbon (i, i + 4); position 6 and 10 | No | Improved: Gram-positive Indifferent: Gram-negative | Increased | Increased | Decreased | [47] |
MPIS-D8N | Polybia-MPI | All-hydrocarbon (i, i + 4); position 6 and 10 | Position 8 D substituted for N | Improved: Gram-positive Indifferent: Gram-negative | Increased | Increased | Decreased | [47] |
MPIS-Q12K | Polybia-MPI | All-hydrocarbon (i, i + 4); position 6 and 10 | Position 12 Q substituted for K | Improved: Gram-positive Indifferent: Gram-negative | Increased | Increased | Decreased | [47] |
Ac-DS-14W | Non-natural alanine/lysine-based | Double all-hydrocarbon in tandem (i, i + 4); positions 2 and 6/9 and 13 | No | Improved: Gram-positive Indifferent: Gram-negative | Increased | Increased | Decreased | [50] |
Ac-DS-5W- | Non-natural alanine/lysine-based (Ac-DS-14W analog) | Double all-hydrocarbon in tandem (i, i + 4); positions 2 and 6/9 and 13 | W insertion at position 5 | Improved | Indifferent | Increased | NA | [50] |
S-6K-F17 | Synthetic peptide 6K-F17 | All-hydrocarbon (i, i + 4); position 10 and 14 | No | Improved | Increased | Increased | NA | [40] |
S-6K-F17-2G | Synthetic peptide 6K-F17 | All-hydrocarbon (i, i + 4); position 10 and 14 | G insertion at positions 8 and 16 | Indifferent | Decreased | Indifferent | NA | [40] |
S-6K-F17-3G | Synthetic peptide 6K-F17 | All-hydrocarbon (i, i + 4); position 10 and 14 | G insertion at positions 8, 13 and 16 | Indifferent | Decreased | Indifferent | NA | [40] |
S-6K-F17-3GN | Synthetic peptide 6K-F17 | All-hydrocarbon (i, i + 4); position 10 and 14 | G insertion at positions 8, 13 and 16 N insertion at position 7 | Indifferent | Decreased | Indifferent | NA | [40] |
Sau-2 | Aurein1.2 | All-hydrocarbon (i, i + 4); position 2 and 6 | No | Improved | NA | Increased | Decreased | [46] |
Peptide 2 | Peptide 1, Mag 2 derivative | All-hydrocarbon (i, i + 4); position 1 and 5 | No | Improved | Decreased | Increased | NA | [26] |
Peptide 8 | Peptide 1, Mag 2 derivative | All-hydrocarbon (i, i + 7); position 8 and 15 | No | Decreased | Increased | Increased | NA | [26] |
Mag (i + 4) 1,15 (A9K) | Mag 2 | Double all-hydrocarbon (i, i + 4); positions 2 and 6/16 and 20 | Position 9 A substituted for K | Improved | Decreased | Increased | Decreased | [51] |
C-MPI-1 | Polybia-MPI | Triazole stapling (i, i + 4); position 8 and 12 | No | Decreased | Increased | Increased | Decreased | [52] |
C-MPI-2 | Polybia-MPI | Triazole stapling (i, i + 6); position 2 and 8 | No | Non-active | NA | Indifferent | NA | [52] |
Peptide 12 (OH-CM6) | OH-CATH30 | Lysine N-alkylation (i, i + 4); position 12 and 16 | No | Improved | Increased, but good therapeutic index | Increased | Decreased | [53] |
V26-SP-8 | VapC26 α454–65 | All-hydrocarbon (i, i + 7); position 1 and 8 | No | Improved | NA | Increased | NA | [54] |
S-TM4 (88–100) | TM4 (88–100) | All-hydrocarbon (i, i + 4); position 4 and 8 | No | Improved | Decreased | Increased | Decreased | [55] |
2.2. Alternative Stapling Strategies
3. Stapling for Protein–Protein Interaction Targets
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Modification Type | Advantages |
---|---|
INSERTION OF D-AMINO ACIDS | ↑ proteolytic stability ↑ membrane insertation |
PEGYLATION | ↑ proteolytic stability ↓ toxicity ↑ biocompatibility ↑ plasma half-live |
ACETYLATION | ↑ proteolytic stability |
DIMERIZATION | ↑ antimicrobial activity ↑ membrane interaction ↑ membrane permeability |
LIPIDATION | ↑ antimicrobial activity ↑ proteolytic stability ↑ membrane permeability ↑ bioavailability |
CYCLIZATION | ↑ antimicrobial activity ↑ proteolytic stability |
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Lourenço, A.L.P.; Rios, T.B.; da Silva, Á.P.; Franco, O.L.; Ramada, M.H.S. Peptide Stapling Applied to Antimicrobial Peptides. Antibiotics 2023, 12, 1400. https://doi.org/10.3390/antibiotics12091400
Lourenço ALP, Rios TB, da Silva ÁP, Franco OL, Ramada MHS. Peptide Stapling Applied to Antimicrobial Peptides. Antibiotics. 2023; 12(9):1400. https://doi.org/10.3390/antibiotics12091400
Chicago/Turabian StyleLourenço, Ana Laura Pereira, Thuanny Borba Rios, Állan Pires da Silva, Octávio Luiz Franco, and Marcelo Henrique Soller Ramada. 2023. "Peptide Stapling Applied to Antimicrobial Peptides" Antibiotics 12, no. 9: 1400. https://doi.org/10.3390/antibiotics12091400