Hybridization with Insect Cecropin A (1–8) Improve the Stability and Selectivity of Naturally Occurring Peptides
Abstract
:1. Introduction
2. Results
2.1. Physicochemical Parameters of Peptides
2.2. Secondary Structures
2.3. Antimicrobial Activity
2.4. Hemolytic Activity and Cytotoxicity of the Peptides
2.5. Cell Selectivity of Peptides
2.6. Salts and Serum Stability
2.7. Outer Membrane Permeabilization
2.8. Cytoplasmic Membrane Depolarization
2.9. Membrane Morphological Analysis
3. Discussion
4. Materials and Methods
4.1. Bacterial Strains and Mammalian Cells
4.2. Peptide Synthesis and Sequence Analysis
4.3. CD Spectroscopy
4.4. Antimicrobial Assays
4.5. Measurement of Hemolytic Activity
4.6. Cytotoxicity Assays
4.7. Calculation of the Therapeutic Index
4.8. Salt and Serum Stability
4.9. Outer Membrane Permeability Assay
4.10. Cytoplasmic Membrane Depolarization Assay
4.11. SEM and TEM Characterization
4.12. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AMR | Antimicrobial resistance |
AMPs | Antimicrobial peptides |
LPS | Lipopolysaccharides |
LTA | Lipoteichoic acids |
MALDI-TOF-MS | Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry |
GRAVY | Grand average of hydropathicity |
CD | Circular dichroism |
PBS | Phosphate-buffered saline |
TFE | Trifluoroethanol |
MICs | The minimum inhibitory concentrations |
MTT | 3-[4,5-dimethylthiozol-2-yl]-2,5-diphenyltetrazolium bromide |
TI | Therapeutic index |
NPN | 1-N-phenylnaphthylamine |
DiSC3–5 | 3,3′-dipropylthiadicarbocyanine |
RP-HPLC | Reverse-phase high performance liquid chromatography |
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Peptide | Sequence | Theoretical Mav (u) | Measured Mav (u) 1 | Purity 2 (%) | Charge | GRAVY 3 |
---|---|---|---|---|---|---|
CA-FO | KWKLFKKIRFGRFLRKIRRFRPK-NH2 | 3104.88 | 3104.24 | 95.72% | +13 | −1.109 |
CA-TP | KWKLFKKIWWPFLRR-NH2 | 2131.66 | 2132.61 | 97.42% | +7 | −0.747 |
CA | KWKLFKKI-NH2 | 1089.42 | 1089.89 | 95.74% | +5 | −0.675 |
FO | RFGRFLRKIRRFRPK-NH2 | 2032.49 | 2032.59 | 99.25% | +9 | −1.340 |
TP | WWPFLRR-NH2 | 1059.27 | 1059.79 | 98.33% | +3 | −0.829 |
MIC (µM) 1 | CA | FO | TP | CA-FO | CA-TP |
---|---|---|---|---|---|
Gram-negative bacteria | |||||
E. coli ATCC25922 | 64 | 32 | 128 | 2 | 2 |
E. coli UB 1005 | >128 | 16 | 128 | 2 | 4 |
S. typhimurium C7731 | >128 | 32 | 64 | 4 | 2 |
S. typhimurium ATCC14028 | >128 | 32 | 32 | 4 | 4 |
P. aeruginosa ATCC27853 | >128 | 32 | 64 | 4 | 4 |
S. pullorum C7913 | >128 | 16 | 64 | 8 | 4 |
Gram-positive bacteria | |||||
S. aureus ATCC29213 | 128 | 64 | 64 | 2 | 2 |
S. epidermidis ATCC12228 | >128 | 16 | 32 | 4 | 2 |
S. faecalis ATCC29212 | >128 | 16 | >128 | 4 | 2 |
Peptide | GM (μM) 1 | HC10 2 | Therapeutic Index (TI) 3 |
---|---|---|---|
CA | 203.19 | 15.54 | 0.08 |
FO | 25.40 | 2.78 | 0.11 |
TP | 74.66 | 25.06 | 0.34 |
CA-FO | 3.43 | 143.34 | 41.79 |
CA-TP | 2.72 | 49.66 | 18.26 |
NaCl 1 | KCl 1 | NH4Cl 1 | MgCl2 1 | ZnCl2 1 | CaCl2 1 | FeCl3 1 | Mix 2 | Control 1 | |
---|---|---|---|---|---|---|---|---|---|
E. coli ATCC 25922 | |||||||||
CA-FO | 32 | 128 | 16 | 8 | 16 | >128 | 8 | >128 | 2 |
CA-TP | 4 | 4 | 1 | 2 | 2 | >128 | 4 | >128 | 2 |
CA | 64 | >128 | >128 | 128 | >128 | >128 | >128 | >128 | 64 |
FO | 32 | 32 | 32 | 16 | 64 | >128 | >128 | >128 | 32 |
TP | 128 | 64 | 128 | 64 | 128 | 64 | 128 | 128 | 64 |
S. aureus ATCC 29213 | |||||||||
CA-FO | 4 | 4 | 2 | 2 | 2 | 1 | 2 | 4 | 2 |
CA-TP | 2 | 2 | 2 | 2 | 2 | 0.25 | 2 | 4 | 2 |
CA | 128 | 128 | >128 | 64 | 64 | 64 | 64 | 64 | 128 |
FO | 32 | 32 | 32 | 16 | 64 | 64 | 64 | 64 | 64 |
TP | 128 | 64 | 128 | 64 | 128 | 64 | 128 | 128 | 64 |
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Yang, Y.; Wu, D.; Wang, C.; Shan, A.; Bi, C.; Li, Y.; Gan, W. Hybridization with Insect Cecropin A (1–8) Improve the Stability and Selectivity of Naturally Occurring Peptides. Int. J. Mol. Sci. 2020, 21, 1470. https://doi.org/10.3390/ijms21041470
Yang Y, Wu D, Wang C, Shan A, Bi C, Li Y, Gan W. Hybridization with Insect Cecropin A (1–8) Improve the Stability and Selectivity of Naturally Occurring Peptides. International Journal of Molecular Sciences. 2020; 21(4):1470. https://doi.org/10.3390/ijms21041470
Chicago/Turabian StyleYang, Yang, Di Wu, Chenxi Wang, Anshan Shan, Chongpeng Bi, Yanbing Li, and Wenping Gan. 2020. "Hybridization with Insect Cecropin A (1–8) Improve the Stability and Selectivity of Naturally Occurring Peptides" International Journal of Molecular Sciences 21, no. 4: 1470. https://doi.org/10.3390/ijms21041470