Abstract
The swift killing kinetics is an attractive characteristics of wide-spectrum antimicrobial activity of peptides, which made them generate great attention as possible antitoxin pharmaceutics for commercial development. Regrettably, and regardless of the significant capability of these composites and the expanded research attempts that were performed to move these compounds to the health care units, the outcome has been finite. Primarily, this is attributed to hurdles associated with the peptides’ low targeting to pathogens and selectivity, exuberant toxicity to human cells, proneness to protease attack, pathogen resistance, and cost of production, poor chemical and physical stability of the peptides, reduced activity based on pH and salt sensitivity, pharmacodynamics and pharmacokinetic issues among others. Protein engineering via rational design and computer-based techniques, such as molecular docking and molecular dynamics simulations, for instance, through amino acid modifications and chemical synthesis, and synergistic effects, has proven to be useful for improving the therapeutic index and antibacterial activity of these artificially made peptides. In this review, we tried to search from the literature and previous scientific findings and researches, to highlight the contribution of modern-day peptide engineering and experimental techniques. In particular, we analyzed rational design, peptide engineering, peptide synthesis, recombinant peptide production, and synergistic effects; and how these methods modulate the peptide and protein functions. It also provides a comprehensive and straightforward overview of several studies towards addressing the issue of some of the limitations affecting these essential compounds that could be efficiently adopted and applied in future investigations.
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This work was supported by a research fund from the Faculty of Science, King Mongkut’s University of Technology Thonburi, KMUTT, and Petch Pra Jom Klao-Ph.D. Scholarship.
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Abbreviations: AMPs, Antimicrobial peptides; HDPs, host defense peptides; MIC, minimum inhibitory concentration; CFU, colony forming unit; MRSA, methicillin-rersistant Staphylococcus aureus; MDR, multidrug resistant; MDRB, multidrug resistant bacteria; MBEC, minimum bactericidal eradication concentration; LPS, lipopolysaccharide; CPP, cell-penetrating peptide; Fmoc, 9-fluorenylmethoxycarbonyl; NiNTA, nickel nitrilotriacetic ncid; GEN, gentamycin; VAN, vancomycin; AZT, azithromycin; AMO, amoxicillin.
Corresponding author: e-mail: nujarin.jon@kmutt.ac.th.
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Ya’u Sabo Ajingi, Nujarin Jongruja Antimicrobial Peptide Engineering: Rational Design, Synthesis, and Synergistic Effect. Russ J Bioorg Chem 46, 463–479 (2020). https://doi.org/10.1134/S1068162020040044
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DOI: https://doi.org/10.1134/S1068162020040044