Abstract
Due to the limited effects of conventional antibiotics on the increasing emergence of drug-resistant bacteria and fungi, novel antimicrobial agents were urgently needed to alleviate this phenomenon. Nowadays, antimicrobial peptides are believed to be a promising candidate for a new generation of antimicrobial drugs. Antimicrobial peptide polybia-MPII (MPII) was first isolated from the venom of the social wasp Polybia paulista with a broad spectrum of antimicrobial activity. In the present study, the counterparts and mimics of cationic amino acids of Lys, such as Arg, His, Orn, Dab and Dap were employed to substitute Lys in the sequence of MPII. The effects of the incorporation of these amino acids on its antimicrobial activity, hemolytic activity, cytotoxicity, enzyme stability and therapeutic potential were explored. Our results showed that although the incorporation of Arg could improve its antimicrobial activity, there is no improvement in enzyme stability. The incorporation of His makes MPII exert its antimicrobial activity in a pH-dependent manner. Notably, incorporating Dap could effectively decrease its hemolytic activity and cytotoxicity and enhance its enzyme stability against trypsin. In conclusion, this study would provide an effective strategy to improve the bioavailability and metabolic stability of AMPs while decrease their hemolytic activity and cytotoxicity.
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Abbreviations
- AMPs:
-
Antimicrobial peptides
- Lys:
-
Lysine
- Arg:
-
Arginine
- MPII:
-
Polybia-MPII
- Orn:
-
L-Ornithine
- Dab:
-
L-2, 4-Diamino butyric acids
- Dap:
-
L-2, 3-Diamino-propionic
- His:
-
L-Histidine
- MBHA:
-
4-Methylbenzhydrylamine
- FMOC:
-
N-9-Fluorenylmethoxycarbonyl
- DMF:
-
Dimethylformamide
- MH:
-
Mueller Hilton broth
- DMEM:
-
Dulbecco's modified eagle medium
- FBS:
-
Fetal bovine serum
- NPN:
-
N-Phenyl-1-napthylamine
- ONPG:
-
O-Nitrophenyl-b-d-galactopyranoside
- MIC:
-
Minimal inhibitory concentration
- MBC:
-
Minimum bactericidal concentration
- CD:
-
Circular dichroism
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (Nos. 82073679, 81960278, 81872723), Natural Science Foundation of Gansu Province, China (No. 20JR5RA245), the Outstanding Youth Funds of Science and Technology Department of Gansu Province (No. 20JR5RA371), and the Fundamental Research Funds for the Central Universities (Nos. lzujbky-2020-kb12, lzujbky-2020-it28).
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KW, WY, and XL designed the research. XL, KL, PZ and JZ prepared the manuscript. KL, PZ, JZ, FZ, YH, HZ, YL, YX and ZZ performed all the experiment. KL and PZ analyzed the data. MF and ZZ revised the manuscript. KW, WY and XL provided financial support.
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Liang, X., Liu, K., Zhao, P. et al. The effects of incorporation of the counterparts and mimics of l-lysine on the antimicrobial activity, hemolytic activity, cytotoxicity and tryptic stability of antimicrobial peptide polybia-MPII. Amino Acids 54, 123–135 (2022). https://doi.org/10.1007/s00726-021-03099-0
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DOI: https://doi.org/10.1007/s00726-021-03099-0