Progress on the design and optimization of antimicrobial peptides_Journal of Biomedical Engineering

Authors：

ZHANG Ruonan ¹ , WU Di ² ,  GAO Yitian ¹

1. School of Life and Environmental Sciences, Wenzhou University, Wenzhou, Zhejiang 325000, P. R. China;
2. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P. R. China;

Corresponding author：

Keywords：

Antimicrobial peptide; Derived peptide; Design and optimization

DOI：

10.7507/1001-5515.202206017

Video：

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Antimicrobial peptides (AMPs) are a class of peptides widely existing in nature with broad-spectrum antimicrobial activity. It is considered as a new alternative to traditional antibiotics because of its unique mechanism of antimicrobial activity. The development and application of natural AMPs are limited due to their drawbacks such as low antimicrobial activity and unstable metabolism. Therefore, the design and optimization of derived peptides based on natural antimicrobial peptides have become recent research hotspots. In this paper, we focus on ribosomal AMPs and summarize the design and optimization strategies of some related derived peptides, which include reasonable primary structure modification, cyclization strategy and computer-aided strategy. We expect to provide ideas for the design and optimization of antimicrobial peptides and the development of anti-infective drugs through analysis and summary in this paper.

Citation： ZHANG Ruonan, WU Di, GAO Yitian. Progress on the design and optimization of antimicrobial peptides. Journal of Biomedical Engineering, 2022, 39(6): 1247-1253. doi: 10.7507/1001-5515.202206017 Copy

1.	Li J, Shang L, Lan J, et al. Targeted and intracellular antibacterial activity against s. agalactiae of the chimeric peptides based on pheromone and cell-penetrating peptides. ACS Applied Materials & Interfaces, 2020, 12(40): 44459-44474.
2.	Lazzaro B P, Zasloff M, Rolff J. Antimicrobial peptides: application informed by evolution. Science, 2020, 368(6490): eaau5480.
3.	Gan B H, Gaynord J, Rowe S M, et al. The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions. Chemical Society reviews. 2021, 50(13): 7820-7880.
4.	Koehbach J, Craik D J. The vast structural diversity of antimicrobial peptides. Trends in Pharmacological Sciences, 2019, 40(7): 517-528.
5.	Koh J J, Lin S, Beuerman R W, et al. Recent advances in synthetic lipopeptides as anti-microbial agents: designs and synthetic approaches. Amino Acids, 2017, 49(10): 1653-1677.
6.	Wang C, Hong T, Cui P, et al. Antimicrobial peptides towards clinical application: delivery and formulation. Adv Drug Deliv Rev, 2021, 175: 113818.
7.	Ting D S J, Beuerman R W, Dua H S, et al. Strategies in translating the therapeutic potentials of host defense peptides. Front Immunol, 2020, 11: 983.
8.	Ramezanzadeh M, Saeedi N, Mesbahfar E, et al. Design and characterization of new antimicrobial peptides derived from aurein 1. 2 with enhanced antibacterial activity. Biochimie, 2021, 181: 42-51.
9.	Schifano N P, Caputo G A. Investigation of the role of hydrophobic amino acids on the structure–activity relationship in the antimicrobial venom peptide ponericin L1. The Journal of Membrane Biology, 2022, 255(4-5): 537-551.
10.	Chen Y, Guarnieri M T, Vasil A I, et al. Role of peptide hydrophobicity in the mechanism of action of alpha-helical antimicrobial peptides. Antimicrobial Agents and Chemotherapy, 2007, 51(4): 1398-1406.
11.	Zhu X, Ma Z, Wang J, et al. Importance of tryptophan in transforming an amphipathic peptide into a pseudomonas aeruginosa-targeted antimicrobial peptide. Plos One, 2014, 9(12): e114605.
12.	Li W, Separovic F, O'Brien-Simpson N M, et al. Chemically modified and conjugated antimicrobial peptides against superbugs. Chemical Society Reviews. 2021, 50(8): 4932-4973.
13.	Agouridas V, El Mahdi O, Diemer V, et al. Native chemical ligation and extended methods: mechanisms, catalysis, scope, and limitations. Chemical Reviews, 2019, 119(12): 7328-7443.
14.	Dwivedi R, Aggarwal P, Bhavesh N S, et al. Design of therapeutically improved analogue of the antimicrobial peptide, indolicidin, using a glycosylation strategy. Amino acids, 2019, 51(10-12): 1443-1460.
15.	Barbosa M, Vale N, Costa F M, et al. Tethering antimicrobial peptides onto chitosan: optimization of azide-alkyne "click" reaction conditions. Carbohydrate Polymers, 2017, 165: 384-393.
16.	Su Y, Tian L, Yu M, et al. Cationic peptidopolysaccharides synthesized by 'click' chemistry with enhanced broad-spectrum antimicrobial activities. Polymer chemistry, 2017. DOI: r10.1039/c7py00528h.
17.	Kamysz E, Sikorska E, Jaśkiewicz M, et al. Lipidated analogs of the LL-37-derived peptide fragment KR12-structural analysis, surface-active properties and antimicrobial activity. Int J Mol Sci, 2020, 21(3): 887.
18.	Wang C, Yang C, Chen Y C, et al. Rational design of hybrid peptides: a novel drug design approach. Curr Med Sci, 2019, 39(3): 349-355.
19.	Xu L, Shao C, Li G, et al. Conversion of broad-spectrum antimicrobial peptides into species-specific antimicrobials capable of precisely targeting pathogenic bacteria. Scientific Reports, 2020, 10(1): 944.
20.	Choudhury A, Islam S M A, Ghidey M R, et al. Repurposing a drug targeting peptide for targeting antimicrobial peptides against Staphylococcus. Biotechnology Letters, 2020, 42(2): 287-294.
21.	Kim H, Jang J H, Kim S C, et al. Development of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa. European Journal of Medicinal Chemistry, 2020, 185: 111814.
22.	He T, Qu R, Zhang J. Current synthetic chemistry towards cyclic antimicrobial peptides. Journal of Peptide Science. 2022, 28(6): e3387.
23.	Buckton L K, Rahimi M N, McAlpine S R. Cyclic peptides as drugs for intracellular targets: the next frontier in peptide therapeutic development. Chemistry, 2021, 27(5): 1487-1513.
24.	Jing X, Jin K. A gold mine for drug discovery: strategies to develop cyclic peptides into therapies. Medicinal Research Reviews, 2020, 40(2): 753-810. .
25.	Mwangi J, Yin Y, Wang G, et al. The antimicrobial peptide ZY4 combats multidrug-resistant pseudomonas aeruginosa and acinetobacter baumannii infection. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116(52): 26516-26522.
26.	Shi G, Kang X, Dong F, et al. DRAMP 3. 0: an enhanced comprehensive data repository of antimicrobial peptides. Nucleic Acids Research, 2021, 50(D1): D488-D496.
27.	Li H, Hu Y, Pu Q, et al. Novel stapling by lysine tethering provides stable and low hemolytic cationic antimicrobial peptides. Journal of Medicinal Chemistry, 2020, 63(8): 4081-4089.
28.	Ramazi S, Mohammadi N, Allahverdi A, et al. A review on antimicrobial peptides databases and the computational tools. Database (Oxford), 2022, 2022: baac011.
29.	Boopathi V, Subramaniyam S, Malik A, et al. mACPpred: a support vector machine-based meta-predictor for identification of anticancer peptides. International Journal of Molecular Sciences, 2019, 20(8): 1964.
30.	Sanner M F, Dieguez L, Forli S, et al. Improving docking power for short peptides using random forest. Journal of Chemical Information and Modeling, 2021, 61(6): 3074-3090.
31.	Waghu F H, Gawde U, Gomatam A, et al. A QSAR modeling approach for predicting myeloid antimicrobial peptides with high sequence similarity. Chemical Biology & Drug Design, 2020, 96(6): 1408-1417.
32.	Long T, McDougal O M, Andersen T. GAMPMS: genetic algorithm managed peptide mutant screening. Journal of Computational Chemistry, 2015, 36(17): 1304-10.
33.	Porto W F, Irazazabal L, Alves E S F, et al. In silico optimization of a guava antimicrobial peptide enables combinatorial exploration for peptide design. Nature communications. 2018, 9(1): 1490.
34.	Di Bonaventura I, Jin X, Visini R, et al. Chemical space guided discovery of antimicrobial bridged bicyclic peptides against Pseudomonas aeruginosa and its biofilms. Chemical Science, 2017, 8(10): 6784-6798.
35.	Di Bonaventura I, Baeriswyl S, Capecchi A, et al. An antimicrobial bicyclic peptide from chemical space against multidrug resistant Gram-negative bacteria. Chemical Communications, 2018, 54(40): 5130-5133.
36.	Heinis C, Rutherford T, Freund S, et al. Phage-encoded combinatorial chemical libraries based on bicyclic peptides. Nature Chemical Biology, 2009, 5(7): 502-507.
37.	Winkler D F H. SPOT synthesis: the solid-phase peptide synthesis on planar surfaces. Methods in Molecular Biology, 2020, 2103: 151-173.
38.	Hilpert K, Volkmer-Engert R, Walter T, et al. High-throughput generation of small antibacterial peptides with improved activity. Nature Biotechnology, 2005, 23(8): 1008-1012.
39.	Salvagni E, García C, Manresa À, et al. Short and ultrashort antimicrobial peptides anchored onto soft commercial contact lenses inhibit bacterial adhesion. Colloids Surf B: Biointerfaces, 2020, 196: 111283.
40.	Liu L, Zhao L, Liu L, et al. Influence of different aromatic hydrophobic residues on the antimicrobial activity and membrane selectivity of BRBR-NH2 tetrapeptide. Langmuir, 2020, 36(50): 15331-15342.
41.	Yadav V, Misra R. A review emphasizing on utility of heptad repeat sequence as a tool to design pharmacologically safe peptide-based antibiotics. Biochimie, 2021, 191: 126-139.
42.	Wang J, Song J, Yang Z, et al. Antimicrobial peptides with high proteolytic resistance for combating Gram-negative bacteria. Journal of Medicinal Chemistry, 2019, 62(5): 2286-2304.
43.	Xu L, Chou S, Wang J, et al. Antimicrobial activity and membrane-active mechanism of tryptophan zipper-like β-hairpin antimicrobial peptides. Amino Acids, 2015, 47(11): 2385-2397.
44.	Zou P, Chen W T, Sun T, et al. Recent advances: peptides and self-assembled peptide-nanosystems for antimicrobial therapy and diagnosis. Biomaterials Science, 2020, 8(18): 4975-4996.
45.	Shen Z, Guo Z, Zhou L, et al. Biomembrane induced in situ self-assembly of peptide with enhanced antimicrobial activity. Biomaterials Science, 2020, 8(7): 2031-2039.

1. Li J, Shang L, Lan J, et al. Targeted and intracellular antibacterial activity against s. agalactiae of the chimeric peptides based on pheromone and cell-penetrating peptides. ACS Applied Materials & Interfaces, 2020, 12(40): 44459-44474.
2. Lazzaro B P, Zasloff M, Rolff J. Antimicrobial peptides: application informed by evolution. Science, 2020, 368(6490): eaau5480.
3. Gan B H, Gaynord J, Rowe S M, et al. The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions. Chemical Society reviews. 2021, 50(13): 7820-7880.
4. Koehbach J, Craik D J. The vast structural diversity of antimicrobial peptides. Trends in Pharmacological Sciences, 2019, 40(7): 517-528.
5. Koh J J, Lin S, Beuerman R W, et al. Recent advances in synthetic lipopeptides as anti-microbial agents: designs and synthetic approaches. Amino Acids, 2017, 49(10): 1653-1677.
6. Wang C, Hong T, Cui P, et al. Antimicrobial peptides towards clinical application: delivery and formulation. Adv Drug Deliv Rev, 2021, 175: 113818.
7. Ting D S J, Beuerman R W, Dua H S, et al. Strategies in translating the therapeutic potentials of host defense peptides. Front Immunol, 2020, 11: 983.
8. Ramezanzadeh M, Saeedi N, Mesbahfar E, et al. Design and characterization of new antimicrobial peptides derived from aurein 1. 2 with enhanced antibacterial activity. Biochimie, 2021, 181: 42-51.
9. Schifano N P, Caputo G A. Investigation of the role of hydrophobic amino acids on the structure–activity relationship in the antimicrobial venom peptide ponericin L1. The Journal of Membrane Biology, 2022, 255(4-5): 537-551.
10. Chen Y, Guarnieri M T, Vasil A I, et al. Role of peptide hydrophobicity in the mechanism of action of alpha-helical antimicrobial peptides. Antimicrobial Agents and Chemotherapy, 2007, 51(4): 1398-1406.
11. Zhu X, Ma Z, Wang J, et al. Importance of tryptophan in transforming an amphipathic peptide into a pseudomonas aeruginosa-targeted antimicrobial peptide. Plos One, 2014, 9(12): e114605.
12. Li W, Separovic F, O'Brien-Simpson N M, et al. Chemically modified and conjugated antimicrobial peptides against superbugs. Chemical Society Reviews. 2021, 50(8): 4932-4973.
13. Agouridas V, El Mahdi O, Diemer V, et al. Native chemical ligation and extended methods: mechanisms, catalysis, scope, and limitations. Chemical Reviews, 2019, 119(12): 7328-7443.
14. Dwivedi R, Aggarwal P, Bhavesh N S, et al. Design of therapeutically improved analogue of the antimicrobial peptide, indolicidin, using a glycosylation strategy. Amino acids, 2019, 51(10-12): 1443-1460.
15. Barbosa M, Vale N, Costa F M, et al. Tethering antimicrobial peptides onto chitosan: optimization of azide-alkyne "click" reaction conditions. Carbohydrate Polymers, 2017, 165: 384-393.
16. Su Y, Tian L, Yu M, et al. Cationic peptidopolysaccharides synthesized by 'click' chemistry with enhanced broad-spectrum antimicrobial activities. Polymer chemistry, 2017. DOI: r10.1039/c7py00528h.
17. Kamysz E, Sikorska E, Jaśkiewicz M, et al. Lipidated analogs of the LL-37-derived peptide fragment KR12-structural analysis, surface-active properties and antimicrobial activity. Int J Mol Sci, 2020, 21(3): 887.
18. Wang C, Yang C, Chen Y C, et al. Rational design of hybrid peptides: a novel drug design approach. Curr Med Sci, 2019, 39(3): 349-355.
19. Xu L, Shao C, Li G, et al. Conversion of broad-spectrum antimicrobial peptides into species-specific antimicrobials capable of precisely targeting pathogenic bacteria. Scientific Reports, 2020, 10(1): 944.
20. Choudhury A, Islam S M A, Ghidey M R, et al. Repurposing a drug targeting peptide for targeting antimicrobial peptides against Staphylococcus. Biotechnology Letters, 2020, 42(2): 287-294.
21. Kim H, Jang J H, Kim S C, et al. Development of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa. European Journal of Medicinal Chemistry, 2020, 185: 111814.
22. He T, Qu R, Zhang J. Current synthetic chemistry towards cyclic antimicrobial peptides. Journal of Peptide Science. 2022, 28(6): e3387.
23. Buckton L K, Rahimi M N, McAlpine S R. Cyclic peptides as drugs for intracellular targets: the next frontier in peptide therapeutic development. Chemistry, 2021, 27(5): 1487-1513.
24. Jing X, Jin K. A gold mine for drug discovery: strategies to develop cyclic peptides into therapies. Medicinal Research Reviews, 2020, 40(2): 753-810. .
25. Mwangi J, Yin Y, Wang G, et al. The antimicrobial peptide ZY4 combats multidrug-resistant pseudomonas aeruginosa and acinetobacter baumannii infection. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116(52): 26516-26522.
26. Shi G, Kang X, Dong F, et al. DRAMP 3. 0: an enhanced comprehensive data repository of antimicrobial peptides. Nucleic Acids Research, 2021, 50(D1): D488-D496.
27. Li H, Hu Y, Pu Q, et al. Novel stapling by lysine tethering provides stable and low hemolytic cationic antimicrobial peptides. Journal of Medicinal Chemistry, 2020, 63(8): 4081-4089.
28. Ramazi S, Mohammadi N, Allahverdi A, et al. A review on antimicrobial peptides databases and the computational tools. Database (Oxford), 2022, 2022: baac011.
29. Boopathi V, Subramaniyam S, Malik A, et al. mACPpred: a support vector machine-based meta-predictor for identification of anticancer peptides. International Journal of Molecular Sciences, 2019, 20(8): 1964.
30. Sanner M F, Dieguez L, Forli S, et al. Improving docking power for short peptides using random forest. Journal of Chemical Information and Modeling, 2021, 61(6): 3074-3090.
31. Waghu F H, Gawde U, Gomatam A, et al. A QSAR modeling approach for predicting myeloid antimicrobial peptides with high sequence similarity. Chemical Biology & Drug Design, 2020, 96(6): 1408-1417.
32. Long T, McDougal O M, Andersen T. GAMPMS: genetic algorithm managed peptide mutant screening. Journal of Computational Chemistry, 2015, 36(17): 1304-10.
33. Porto W F, Irazazabal L, Alves E S F, et al. In silico optimization of a guava antimicrobial peptide enables combinatorial exploration for peptide design. Nature communications. 2018, 9(1): 1490.
34. Di Bonaventura I, Jin X, Visini R, et al. Chemical space guided discovery of antimicrobial bridged bicyclic peptides against Pseudomonas aeruginosa and its biofilms. Chemical Science, 2017, 8(10): 6784-6798.
35. Di Bonaventura I, Baeriswyl S, Capecchi A, et al. An antimicrobial bicyclic peptide from chemical space against multidrug resistant Gram-negative bacteria. Chemical Communications, 2018, 54(40): 5130-5133.
36. Heinis C, Rutherford T, Freund S, et al. Phage-encoded combinatorial chemical libraries based on bicyclic peptides. Nature Chemical Biology, 2009, 5(7): 502-507.
37. Winkler D F H. SPOT synthesis: the solid-phase peptide synthesis on planar surfaces. Methods in Molecular Biology, 2020, 2103: 151-173.
38. Hilpert K, Volkmer-Engert R, Walter T, et al. High-throughput generation of small antibacterial peptides with improved activity. Nature Biotechnology, 2005, 23(8): 1008-1012.
39. Salvagni E, García C, Manresa À, et al. Short and ultrashort antimicrobial peptides anchored onto soft commercial contact lenses inhibit bacterial adhesion. Colloids Surf B: Biointerfaces, 2020, 196: 111283.
40. Liu L, Zhao L, Liu L, et al. Influence of different aromatic hydrophobic residues on the antimicrobial activity and membrane selectivity of BRBR-NH2 tetrapeptide. Langmuir, 2020, 36(50): 15331-15342.
41. Yadav V, Misra R. A review emphasizing on utility of heptad repeat sequence as a tool to design pharmacologically safe peptide-based antibiotics. Biochimie, 2021, 191: 126-139.
42. Wang J, Song J, Yang Z, et al. Antimicrobial peptides with high proteolytic resistance for combating Gram-negative bacteria. Journal of Medicinal Chemistry, 2019, 62(5): 2286-2304.
43. Xu L, Chou S, Wang J, et al. Antimicrobial activity and membrane-active mechanism of tryptophan zipper-like β-hairpin antimicrobial peptides. Amino Acids, 2015, 47(11): 2385-2397.
44. Zou P, Chen W T, Sun T, et al. Recent advances: peptides and self-assembled peptide-nanosystems for antimicrobial therapy and diagnosis. Biomaterials Science, 2020, 8(18): 4975-4996.
45. Shen Z, Guo Z, Zhou L, et al. Biomembrane induced in situ self-assembly of peptide with enhanced antimicrobial activity. Biomaterials Science, 2020, 8(7): 2031-2039.

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