Concerns in the Design and Development of Novel Antimicrobial Peptides
Trends in Peptide and Protein Sciences,
Vol. 1 No. 4 (2017),
3 September 2017
,
Page 135-143
https://doi.org/10.22037/tpps.v1i4.16328
Abstract
Peptide and protein based therapeutics are the most promising approaches in today medicine. Bioactive peptides can be valuable drugs in the treatment of various illnesses, such as cardiovascular and neurodegenerative diseases. Cell toxic peptides can be considered for cancer or infection therapy. Antimicrobial peptides (AMPs) are one of the most interesting antibiotic groups in this regard, especially in drug resistance infections. Numerous AMPs have been discovered from the natural source; however, artificial synthetic ones have been also developed based on rational design or bioinformatics modeling. Physicochemical features of AMPs are highly important in their antibacterial activity as well as their toxicity. The best AMP is the one that has selective potent antimicrobial bioactivity and no or least hemolytic and cytotoxic effect. In this review, various structural factors affecting the AMPs bioactivity, such as AMPs size, charge, amphipathicity, and amino acid sequence are illustrated considering the most recently published articles. Finally, the trends in AMP design and development are discussed.
HIGHLIGHTS
•Antimicrobial peptides are highly interesting antibiotics in multi-drug resistance infections.
•Antimicrobial peptides are short peptides with less than 50 amino acids and overall positive charge.
•First and second structural features of AMPs are important factors in their bioactivities.
•Cyclization and branching of AMPs could affect their pharmacokinetic and pharmacodynamics.
- Antimicrobial Peptide
- Computational Tools
- Rational Design
- Activity Improvement
How to Cite
References
Abraham, T., Prenner, E. J., Lewis, R. N. A. H., Mant, C. T., Keller, S., Hodges, R. S. and R. N. McElhaney, (2014). ″Structure-activity relationships of the antimicrobial peptide gramicidin S and its analogs: Aqueous solubility, self-association, conformation, antimicrobial activity and interaction with model lipid membranes.″ Biochimica et Biophysica Acta - Biomembranes, 1838 (5): 1420-1429. doi: 10.1016/j.bbamem.2013.12.019
Alvarez-Ordóñez, A., Begley, M., Clifford, T., Deasy, T., Considine, K. and C. Hill, (2013). ″Structure-activity relationship of synthetic variants of the milk-derived antimicrobial peptide αs2-casein f(183-207).″ Applied and Environmental Microbiology, 79 (17): 5179-5185. doi: 10.1128/aem.01394-13
Andreev, K., Martynowycz, M. W., Ivankin, A., Huang, M. L., Kuzmenko, I., Meron, M., Lin, B., Kirshenbaum, K. and D. Gidalevitz, (2016). ″Cyclization Improves Membrane Permeation by Antimicrobial Peptoids.″ Langmuir, 32(48): 12905-12913.
Astafieva, A., Rogozhin, E., Odintsova, T., Khadeeva, N., Grishin, E. and T. A. Egorov, (2012). Discovery of novel antimicrobial peptides with unusual cysteine motifs in dandelion Taraxacum officinale Wigg. flowers. Peptides, 36 (2): 266-271.
zmi, F., Elliott, A. G., Marasini, N., Ramu, S., Ziora, Z., Kavanagh, A. M., Blaskovich, M. A., Cooper, M. A., Skwarczynski, M. and I. Toth, (2016). ″Short cationic lipopeptides as effective antibacterial agents: Design, physicochemical properties and biological evaluation.″ Bioorganic & Medicinal Chemistry, 24 (10): 2235-2241. doi: http://dx.doi.org/10.1016/j.bmc.2016.03.053
Badosa, E., Ferre, R., Planas, M., Feliu, L., Besalú, E., Cabrefiga, J., Bardají, E. and E. Montesinos, (2007). ″A library of linear undecapeptides with bactericidal activity against phytopathogenic bacteria.″ Peptides, 28 (12): 2276-2285. doi: 10.1016/j.peptides.2007.09.010
Bahar, A. A. and D. Ren, (2013). "Antimicrobial peptides." Pharmaceuticals, 6 (12): 1543-1575.
Blondelle, S. E. and K. Lohner, (2010). ″Optimization and high-throughput screening of antimicrobial peptides.″ Current Pharmaceutical Design, 16 (28): 3204-3211. doi: 10.2174/138161210793292438
Brook, M., Tomlinson, G. H., Miles, K., Smith, R. W., Rossi, A. G., Hiemstra, P. S., van’t Wout, E. F., Dean, J. L., Gray, N. K., Lu, W. and M. Gray, (2016). ″Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage mRNA translation.″ Proceedings of the National Academy of Sciences, 113 (16): 4350-4355.
Chen, H. L., Su, P. Y. and C. Shih, (2016). ″Improvement of in vivo antimicrobial activity of HBcARD peptides by D-arginine replacement.″ Applied Microbiology and Biotechnology, 100 (21): 9125-32.
Currie, S.M., Findlay, E. G., McFarlane, A. J., Fitch, P. M., Böttcher, B., Colegrave, N., Paras, A., Jozwik, A., Chiu, C., Schwarze, J. and D. J. Davidson, (2016). ″Cathelicidins have direct antiviral activity against respiratory syncytial virus in vitro and protective function in vivo in mice and humans.″ The Journal of Immunology, 196 (6): 2699-2710.
Domalaon, R., G Zhanel, G. and F. Schweizer, (2016). ″Short antimicrobial peptides and peptide scaffolds as promising antibacterial agents.″ Current Topics in Medicinal Chemistry, 16 (11): 1217-1230.
Fjell, C. D., Hancock, R. E. W. and H. Jenssen, (2010). ″Computer-aided design of antimicrobial peptides.″ Current Pharmaceutical Analysis, 6 (2): 66-75. doi: 10.2174/157341210791202645
Fjell, C. D., Hiss, J. A., Hancock, R. E. W. and G. Schneider, (2012). ʺDesigning antimicrobial peptides: Form follows function.ʺ Nature Reviews Drug Discovery, 11 (1): 37-51. doi: 10.1038/nrd3591
Giuliani, A., Pirri, G. and S. Nicoletto, (2007). ʺAntimicrobial peptides: an overview of a promising class of therapeutics.″ Open Life Sciences, 2 (1): 1-33.
Gordon, Y. J., Romanowski, E. G. and A. M. McDermott, (2005). ″A review of antimicrobial peptides and their therapeutic potential as anti-infective drugs.ʺ Current Eye Research, 30 (7): 505-515.
Hancock, R. E. (2001). ʺCationic peptides: effectors in innate immunity and novel antimicrobials.ʺ The Lancet infectious diseases, 1 (3): 156-164.
Hancock, R. E., Haney, E. F. and E. E. Gill, (2016). ″The immunology of host defence peptides: beyond antimicrobial activity.″ Nature Reviews Immunology, 16: 321–334.
Haney, E. F., Nazmi, K., Bolscher, J. G. M. and H. J. Vogel, (2012). ″Structural and biophysical characterization of an antimicrobial peptide chimera comprised of lactoferricin and lactoferrampin.″ Biochimica et Biophysica Acta - Biomembranes, 1818 (3): 762-775. doi: 10.1016/j.bbamem.2011.11.023
Hansen, A. M., Bonke, G., Larsen, C. J., Yavari, N., Nielsen, P. E. and H. Franzyk, (2016). ʺAntibacterial Peptide Nucleic Acid–Antimicrobial Peptide (PNA–AMP) Conjugates: Antisense Targeting of Fatty Acid Biosynthesis.ʺ Bioconjugate Chemistry, 27 (4): 863-867.
Jiang, Z., Vasil, A. I., Hale, J. D., Hancock, R. E., Vasil, M. L. and R. S. Hodges, (2008). ″Effects of net charge and the number of positively charged residues on the biological activity of amphipathic α‐helical cationic antimicrobial peptides.″ Peptide Science, 90 (3): 369-383.
Jung, S., Mysliwy, J., Spudy, B., Lorenzen, I., Reiss, K., Gelhaus, C., Podschun, R., Leippe, M. and J. Grötzinger, (2011). ″Human β-defensin 2 and β-defensin 3 chimeric peptides reveal the structural basis of the pathogen specificity of their parent molecules.″ Antimicrobial Agents and Chemotherapy, 55 (3): 954-960.
Juretić, D., Vukičević, D. and A. Tossi, (2017). ″Tools for Designing Amphipathic Helical Antimicrobial Peptides.″ Antimicrobial Peptides: Methods and Protocols, 1548: 23-34.
Khara, J. S., Lim, F. K., Wang, Y., Ke, X. Y., Voo, Z. X., Yang, Y. Y., Lakshminarayanan, R. and P. L. R. Ee, (2015). ″Designing α-helical peptides with enhanced synergism and selectivity against Mycobacterium smegmatis: Discerning the role of hydrophobicity and helicity.″ Acta Biomaterialia, 28: 99-108.
Khara, J. S., Priestman, M., Uhía, I., Hamilton, M. S., Krishnan, N., Wang, Y., Yang, Y. Y., Langford, P. R., Newton, S. M., Robertson, B. D. and P. L. R. Ee, (2016). ″Unnatural amino acid analogues of membrane-active helical peptides with anti-mycobacterial activity and improved stability.″ Journal of Antimicrobial Chemotherapy, 71 (8): 2181-2191.
Kim, H., Jang, J. H., Kim, S. C. and J. H. Cho, (2014). ″De novo generation of short antimicrobial peptides with enhanced stability and cell specificity.″ Journal of Antimicrobial Chemotherapy, 69(1): 121-132.
Lam, S. J., O'Brien-Simpson, N. M., Pantarat, N., Sulistio, A., Wong, E. H., Chen, Y. Y., Lenzo, J. C., Holden, J. A., Blencowe, A., Reynolds, E. C. and G. G. Qiao, (2016). ″Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers.″ Nature microbiology, 1: 16162.
Lashua, L. P., Melvin, J. A., Deslouches, B., Pilewski, J. M., Montelaro, R. C. and J. M. Bomberger, (2016). ″Engineered cationic antimicrobial peptide (eCAP) prevents Pseudomonas aeruginosa biofilm growth on airway epithelial cells.″ Journal of Antimicrobial Chemotherapy, 71 (8): 2200-2207.
Lee, J. k., Seo, C. H., Luchian, T. and Y. Park, (2016). ʺAntimicrobial Peptide CMA3 Derived from the CA-MA Hybrid Peptide: Antibacterial and Anti-inflammatory Activities with Low Cytotoxicity and Mechanism of Action in Escherichia coli.″ Antimicrobial agents and chemotherapy, 60 (1): 495-506.
Lee, T. H., N Hall, K. and M. I. Aguilar, (2016). ″Antimicrobial peptide structure and mechanism of action: a focus on the role of membrane structure.″ Current Topics in Medicinal Chemistry, 16 (1): 25-39.
Liu, D., Liu, J., Wang, W., Xia, L., Yang, J., Sun, S. and F. Zhang, (2016). ″Computational and Experimental Investigation of the Antimicrobial Peptide Cecropin XJ and its Ligands as the Impact Factors of Antibacterial Activity.″ Food Biophysics, 11 (4): 319-331.
López-García, B., Pérez-Payá, E. and J. F. Marcos, (2002). ″Identification of novel hexapeptides bioactive against phytopathogenic fungi through screening of a synthetic peptide combinatorial library.″ Applied and Environmental Microbiology, 68 (5): 2453-2460.
Madsen, J. L., Hjørringgaard, C. U., Vad, B. S., Otzen, D. and T. Skrydstrup, (2016). ʺIncorporation of β‐Silicon‐β3‐Amino Acids in the Antimicrobial Peptide Alamethicin Provides a 20‐Fold Increase in Membrane Permeabilization.ʺ Chemistry-A European Journal, 22 (24): 8358-8367.
Mangoni, M. L., McDermott, A. M. and M. Zasloff, (2016). ʺAntimicrobial peptides and wound healing: biological and therapeutic considerations.ʺ Experimental dermatology, 25 (3): 167-173.
Marani, M. M., Perez, L. O., de Araujo, A. R., Plácido, A., Sousa, C. F., Quelemes, P. V., Oliveira, M., Gomes-Alves, A. G., Pueta, M., Gameiro, P. and A. M. Tomás, (2017). ʺThaulin-1: The first antimicrobial peptide isolated from the skin of a Patagonian frog Pleurodema thaul (Anura: Leptodactylidae: Leiuperinae) with activity against Escherichia coli.ʺ Gene, 605: 70-80. doi: http://dx.doi.org/10.1016/j.gene.2016.12.020
Methatham, T., Boonchuen, P., Jaree, P., Tassanakajon, A. and K. Somboonwiwat, (2017). ʺAntiviral action of the antimicrobial peptide ALFPm3 from Penaeus monodon against white spot syndrome virus.″ Developmental & Comparative Immunology, 69: 23-32.
Muhammad, T., Gunasekera, S., Strömstedt, A. and U. Göransson, (2016). ″Engineering of KR-12: A minimalized domain derived from human host defense peptide LL-37 into a potent antimicrobial drug lead.″ Planta Medica, 81 (S01): P736.
Murayama, T., Pujals, S., Hirose, H., Nakase, I. and S. Futaki, (2016). ″Effect of amino acid substitution in the hydrophobic face of amphiphilic peptides on membrane curvature and perturbation: N‐terminal helix derived from adenovirus internal protein VI as a model.″ Peptide Science, 106 (4): 430-439.
Nishikawa, T., Nakagami, H., Maeda, A., Morishita, R., Miyazaki, N., Ogawa, T., Tabata, Y., Kikuchi, Y., Hayashi, H., Tatsu, Y. and N. Yumoto, (2009). ″Development of a novel antimicrobial peptide, AG‐30, with angiogenic properties.″ Journal of Cellular and Molecular Medicine, 13 (3): 535-546.
Novković, M., Simunić, J., Bojović, V., Tossi, A. and D. Juretić, (2012). ″DADP: the database of anuran defense peptides.″ Bioinformatics, 28 (10): 1406-1407.
ovoa, B., Romero, A., Álvarez, Á. L., Moreira, R., Pereiro, P., Costa, M. M., Dios, S., Estepa, A., Parra, F. and A. Figueras, (2016). ″Antiviral activity of myticin C peptide from mussel: an ancient defence against herpesviruses.″ Journal of Virology, 90 (17):7692-702.
Ong, Z. Y., Wiradharma, N. and Y. Y. Yang, (2014). ″Strategies employed in the design and optimization of synthetic antimicrobial peptide amphiphiles with enhanced therapeutic potentials.″ Advanced drug delivery reviews, 78: 28-45.
Pane, K., Sgambati, V., Zanfardino, A., Smaldone, G., Cafaro, V., Angrisano, T., Pedone, E., Di Gaetano, S., Capasso, D., Haney, E. F. and V. Izzo, (2016). ″A new cryptic cationic antimicrobial peptide from human apolipoprotein E with antibacterial activity and immunomodulatory effects on human cells.″ The FEBS journal, 283 (11): 2115-2131.
Park, C. H., Valore, E. V., Waring, A. J. and T. Ganz, (2001). ″Hepcidin, a urinary antimicrobial peptide synthesized in the liver.″ Journal of Biological Chemistry, 276 (11): 7806-7810.
Pearson, C. S., Kloos, Z., Murray, B., Tabe, E., Gupta, M., Kwak, J. H., Karande, P., McDonough, K. A. and G. Belfort, (2016). ″Combined bioinformatic and rational design approach to develop antimicrobial peptides against Mycobacterium tuberculosis.″ Antimicrobial Agents and Chemotherapy, 60 (5): 2757-2764.
Pedron, C. N., Torres, M. D. T., da Silva Lima, J. A., Silva, P. I., Silva, F. D. and V. X. Oliveira, (2017). ″Novel designed VmCT1 analogs with increased antimicrobial activity.″ European Journal of Medicinal Chemistry, 126: 456-463.
Petit, V. W., Rolland, J. L., Blond, A., Cazevieille, C., Djediat, C., Peduzzi, J., Goulard, C., Bachère, E., Dupont, J., Destoumieux-Garzón, D. and S. Rebuffat, (2016). ″A hemocyanin-derived antimicrobial peptide from the penaeid shrimp adopts an alpha-helical structure that specifically permeabilizes fungal membranes.″ Biochimica et Biophysica Acta (BBA) - General Subjects, 1860 (3): 557-568. doi: http://dx.doi.org/10.1016/j.bbagen.2015.12.010
Pires, J., Siriwardena, T. N., Stach, M., Tinguely, R., Kasraian, S., Luzzaro, F., Leib, S. L., Darbre, T., Reymond, J. L. and A. Endimiani, (2015). ″In vitro activity of the novel antimicrobial peptide dendrimer G3KL against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa.″ Antimicrobial Agents and Chemotherapy, 59 (12): 7915-7918.
Prada, Y. A., Guzmán, F., Rondón, P., Escobar, P., Ortíz, C., Sierra, D. A., Torres, R. and E. Mejía-Ospino, (2016). ″A New Synthetic Peptide with In vitro Antibacterial Potential Against Escherichiacoli O157: H7 and Methicillin-Resistant Staphylococcusaureus (MRSA).″ Probiotics and Antimicrobial Proteins, 8 (3): 134-140.
Qiao, K., Xu, W. F., Chen, H. Y., Peng, H., Zhang, Y. Q., Huang, W. S., Wang, S. P., An, Z., Shan, Z. G., Chen, F. Y. and K. J. Wang, (2016). ″A new antimicrobial peptide SCY2 identified in Scylla Paramamosain exerting a potential role of reproductive immunity.″ Fish & shellfish immunology, 51: 251-262.
Sajjan, U. S., Tran, L. T., Sole, N., Rovaldi, C., Akiyama, A., Friden, P. M., Forstner, J. F. and D. M. Rothstein, (2001). ″P-113d, an Antimicrobial Peptide Active againstPseudomonas aeruginosa, Retains Activity in the Presence of Sputum from Cystic Fibrosis Patients.″ Antimicrobial agents and chemotherapy, 45 (12): 3437-3444.
Shan, Z., Zhu, K., Peng, H., Chen, B., Liu, J., Chen, F., Ma, X., Wang, S., Qiao, K. and K. Wang, (2016). ″The New Antimicrobial Peptide SpHyastatin from the Mud Crab Scylla paramamosain with Multiple Antimicrobial Mechanisms and High Effect on Bacterial Infection.″ Frontiers in Microbiology, 7: 1140. doi: 10.3389/fmicb.2016.01140.
Sharma, A., Gupta, P., Kumar, R. and A. Bhardwaj, (2016). ″dPABBs: A Novel in silico Approach for Predicting and Designing Anti-biofilm Peptides.″ Scientific Reports, 6: 21839. doi: 10.1038/srep21839
Silva, O. N., de la Fuente-Núñez, C., Haney, E. F., Fensterseifer, I. C. M., Ribeiro, S. M., Porto, W. F., Brown, P., Faria-Junior, C., Rezende, T. M. B., Moreno, S. E. and Lu, T. K. (2016). ″An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities.″ Scientific Reports, 6: 35465. doi: 10.1038/srep35465.
Sørensen, O. E. (2016). ″Antimicrobial Peptides in Cutaneous Wound Healing″. In: Harder, J. and j. M. Schröder (ED), Antimicrobial Peptides, Springer International Publishing, Switzerland, pp. 1-15.
Stach, M., Maillard, N., Kadam, R. U., Kalbermatter, D., Meury, M., Page, M. G., Fotiadis, D., Darbre, T. and J. L. Reymond, (2012). ″Membrane disrupting antimicrobial peptide dendrimers with multiple amino termini.″ Medicinal Chemical Communications, 3(1): 86-89.
Stach, M., Siriwardena, T. N., Köhler, T., Van Delden, C., Darbre, T. and J. L. Reymond, (2014). ″Combining Topology and Sequence Design for the Discovery of Potent Antimicrobial Peptide Dendrimers against Multidrug‐Resistant Pseudomonas aeruginosa.″ Angewandte Chemie International Edition, 53 (47): 12827-12831.
Torcato, I. M., Huang, Y.-H., Franquelim, H. G., Gaspar, D., Craik, D. J., Castanho, M. A. and S. T. Henriques, (2013). ″Design and characterization of novel antimicrobial peptides, R-BP100 and RW-BP100, with activity against Gram-negative and Gram-positive bacteria.″ Biochimica et Biophysica Acta (BBA)-Biomembranes, 1828 (3): 944-955.
Vale, N., Aguiar, L. and P. Gomes, (2014). ″Antimicrobial peptides: a new class of antimalarial drugs?″ Frontiers in pharmacology, 5: 275.
van Dijk, A., van Eldik, M., Veldhuizen, E. J., Tjeerdsma-van Bokhoven, H. L., de Zoete, M. R., Bikker, F. J. and H. P. Haagsman, (2016). ″Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides.″ PLoS One, 11(2): e0147919.
Waghu, F. H., Barai, R. S., Gurung, P. and S. Idicula-Thomas, (2015). ″CAMPR3: a database on sequences, structures and signatures of antimicrobial peptides.″ Nucleic acids research, 44 (D1): D1094-D1097. doi: https://doi.org/10.1093/nar/gkv1051.
Wang, G. (2014). ″Human antimicrobial peptides and proteins.ʺ Pharmaceuticals, 7 (5): 545-594.
Wang, G. (2015). ʺImproved methods for classification, prediction, and design of antimicrobial peptides.″ Computational Peptidology: Methods in Molecular Biology, 1268: 43-66.
Wessolowski, A., Bienert, M. and M. Dathe, (2004). ″Antimicrobial activity of arginine‐and tryptophan‐rich hexapeptides: the effects of aromatic clusters, d‐amino acid substitution and cyclization.″ The Journal of peptide research, 64 (4): 159-169.
Yang, N., Wang, X., Teng, D., Mao, R., Hao, Y., Zong, L., Feng, X. and J. Wang, (2016). ″Modification and characterization of a new recombinant marine antimicrobial peptide N2.ʺ Process Biochemistry, 51(6): 734-739. doi: http://dx.doi.org/10.1016/j.procbio.2016.03.005
Zhang, S. K., Song, J. W., Gong, F., Li, S. B., Chang, H. Y., Xie, H. M., Gao, H. W., Tan, Y. X. and S. P. Ji, (2016). ʺDesign of an α-helical antimicrobial peptide with improved cell-selective and potent anti-biofilm activity.ʺ Scientific Reports, 6: 27394. doi: 10.1038/srep27394.
Zhu, X., Ma, Z., Wang, J., Chou, S. and A. Shan, (2014). ″Importance of tryptophan in transforming an amphipathic peptide into a Pseudomonas aeruginosa-targeted antimicrobial peptide.″ PloS one, 9(12): e114605.
Zhu, X., Zhang, L., Wang, J., Ma, Z., Xu, W., Li, J. and A. Shan, (2015). ″Characterization of antimicrobial activity and mechanisms of low amphipathic peptides with different α-helical propensity.″ Acta Biomaterialia, 18: 155-167.
Zasloff, M. (2016). ″Antimicrobial Peptides: Do They Have a Future as Therapeutics?″ In: Harder, J. and j. M. Schröder (ED), Antimicrobial Peptides, Springer International Publishing, Switzerland, pp. 147-154.
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