Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PLpro Protein
Abstract
:1. Introduction
2. Materials and Methods
2.1. Peptides Synthesis
2.2. Determination of the Minimum Inhibitory Concentration and Minimum Bactericidal Concentration
2.3. Hemolysis Assay
2.4. Circular Dichroism Spectroscopy
2.5. Permeability in Different Vesicle Compositions
2.6. PLpro Inhibition
3. Results and Discussion
3.1. Peptide Synthesis
3.2. Biological Activity
3.3. Hemolysis Assay
3.4. Circular Dichroism
3.5. Vesicle Permeabilization
3.6. Inhibition of SARS-CoV-2 PLpro Enzymatic Activity
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Peptides | S. aureus ATCC 25923 | S. epidermidis ATCC 35984 | E. faecalis ATCC 29212 | E. faecium ATCC 700221 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
MIC μg/mL | MIC µM | MBC μg/mL | Act | MIC μg/mL | MIC µM | MBC μg/mL | Act | MIC μg/mL | MIC µM | MBC μg/mL | Act | MIC μg/mL | MIC µM | MBC μg/mL | Act | |
L-monomer | >512 | >371 | >512 | ND | >512 | >371 | >512 | ND | >512 | >371 | >512 | ND | >512 | >371 | >512 | ND |
D-monomer | >512 | >371 | >512 | ND | >512 | >371 | >512 | ND | >512 | >371 | >512 | ND | >512 | >371 | >512 | ND |
L-dimer | 32 | 11 | 128 | Bc | 8 | 2 | 16 | Bc | 64 | 22 | 128 | Bc | 16 | 5 | >64 | Bs |
D-dimer | 256 | 89 | >512 | ND | 16 | 5 | 16 | Bc | 512 | 178 | 512 | Bc | 64 | 22 | >256 | Bs |
L-tetramer | 64 | 10 | 256 | Bc | 16 | 2 | 32 | Bc | 64 | 10 | 128 | Bc | 16 | 2 | 32 | Bc |
D-tetramer | 64 | 10 | 64 | Bc | 16 | 2 | 16 | Bc | 32 | 5 | 32 | Bc | 16 | 2 | 16 | Bc |
Peptides | K. pneumoniae ATCC 700603 | E. coli ATCC 25922 | A. baumannii ATCC 19606 | P. aeruginosa ATCC 27853 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
MIC μg/mL | MIC µM | MBC μg/mL | Act | MIC μg/mL | MIC µM | MBC μg/mL | Act | MIC μg/mL | MIC µM | MBC μg/mL | Act | MIC μg/mL | MIC µM | MBC μg/mL | Act | |
L-monomer | >512 | >371 | >512 | ND | >512 | >371 | >512 | ND | >512 | >371 | >512 | ND | >512 | >371 | >512 | ND |
D-monomer | 512 | 371 | 512 | Bc | 256 | 185 | 256 | Bc | >512 | >371 | >512 | ND | >512 | >371 | >512 | ND |
L-dimer | >128 | >44 | ND | ND | 32 | 11 | 64 | Bc | 256 | 89 | >512 | ND | >512 | >178 | ND | ND |
D-dimer | 64 | 22 | 128 | Bc | 32 | 11 | 32 | Bc | 16 | 5 | 64 | Bc | 256 | 89 | 512 | Bc |
L-tetramer | 32 | 5 | >128 | Bs | 32 | 5 | >128 | Bs | 32 | 5 | 64 | Bc | 32 | 5 | 64 | Bc |
D-tetramer | 32 | 5 | 32 | Bc | 32 | 5 | >128 | Bs | 32 | 5 | 32 | Bc | 32 | 5 | 64 | Bc |
Peptide | Inhibition (%) at 10 µM | IC50 μM |
---|---|---|
L-monomer | 93.30 ± 0.00 | 2.1 ± 0.1 |
D-monomer | 85.00 ± 3.00 | 3.0 ± 1 |
L-dimer * | 98.05 ± 1.62 | 2.4 ± 0.1 |
D-dimer * | 96.35 ± 0.91 | 1.30 ± 0.03 |
L-tetramer * | 98.40 ± 0.00 | 1.40 ± 0.02 |
D-tetramer | 94.00 ± 3.00 | 2.7 ± 0.5 |
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Bitencourt, N.V.; Righetto, G.M.; Camargo, I.L.B.C.; de Godoy, M.O.; Guido, R.V.C.; Oliva, G.; Santos-Filho, N.A.; Cilli, E.M. Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PLpro Protein. Pharmaceutics 2023, 15, 436. https://doi.org/10.3390/pharmaceutics15020436
Bitencourt NV, Righetto GM, Camargo ILBC, de Godoy MO, Guido RVC, Oliva G, Santos-Filho NA, Cilli EM. Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PLpro Protein. Pharmaceutics. 2023; 15(2):436. https://doi.org/10.3390/pharmaceutics15020436
Chicago/Turabian StyleBitencourt, Natália Vitória, Gabriela Marinho Righetto, Ilana Lopes Baratella Cunha Camargo, Mariana Ortiz de Godoy, Rafael Victorio Carvalho Guido, Glaucius Oliva, Norival Alves Santos-Filho, and Eduardo Maffud Cilli. 2023. "Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PLpro Protein" Pharmaceutics 15, no. 2: 436. https://doi.org/10.3390/pharmaceutics15020436
APA StyleBitencourt, N. V., Righetto, G. M., Camargo, I. L. B. C., de Godoy, M. O., Guido, R. V. C., Oliva, G., Santos-Filho, N. A., & Cilli, E. M. (2023). Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PLpro Protein. Pharmaceutics, 15(2), 436. https://doi.org/10.3390/pharmaceutics15020436