Antimicrobial Peptide Mimics for Clinical Use: Does Size Matter?
The search for efficient antimicrobial therapies that can alleviate suffering caused by infections from resistant bacteria is more urgent than ever before. Infections caused by multi-resistant pathogens represent a significant and increasing burden to healthcare and society and researcher are invest...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.915368/full |
| _version_ | 1828731631659122688 |
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| author | Johan Svenson Natalia Molchanova Christina I. Schroeder |
| author_facet | Johan Svenson Natalia Molchanova Christina I. Schroeder |
| author_sort | Johan Svenson |
| collection | DOAJ |
| description | The search for efficient antimicrobial therapies that can alleviate suffering caused by infections from resistant bacteria is more urgent than ever before. Infections caused by multi-resistant pathogens represent a significant and increasing burden to healthcare and society and researcher are investigating new classes of bioactive compounds to slow down this development. Antimicrobial peptides from the innate immune system represent one promising class that offers a potential solution to the antibiotic resistance problem due to their mode of action on the microbial membranes. However, challenges associated with pharmacokinetics, bioavailability and off-target toxicity are slowing down the advancement and use of innate defensive peptides. Improving the therapeutic properties of these peptides is a strategy for reducing the clinical limitations and synthetic mimics of antimicrobial peptides are emerging as a promising class of molecules for a variety of antimicrobial applications. These compounds can be made significantly shorter while maintaining, or even improving antimicrobial properties, and several downsized synthetic mimics are now in clinical development for a range of infectious diseases. A variety of strategies can be employed to prepare these small compounds and this review describes the different compounds developed to date by adhering to a minimum pharmacophore based on an amphiphilic balance between cationic charge and hydrophobicity. These compounds can be made as small as dipeptides, circumventing the need for large compounds with elaborate three-dimensional structures to generate simplified and potent antimicrobial mimics for a range of medical applications. This review highlight key and recent development in the field of small antimicrobial peptide mimics as a promising class of antimicrobials, illustrating just how small you can go. |
| first_indexed | 2024-04-12T17:48:13Z |
| format | Article |
| id | doaj.art-9348f8020e964c8895b73d47d529e3d3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T17:48:13Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9348f8020e964c8895b73d47d529e3d32022-12-22T03:22:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.915368915368Antimicrobial Peptide Mimics for Clinical Use: Does Size Matter?Johan Svenson0Natalia Molchanova1Christina I. Schroeder2Cawthron Institute, Nelson, New ZealandThe Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, United StatesCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, United StatesThe search for efficient antimicrobial therapies that can alleviate suffering caused by infections from resistant bacteria is more urgent than ever before. Infections caused by multi-resistant pathogens represent a significant and increasing burden to healthcare and society and researcher are investigating new classes of bioactive compounds to slow down this development. Antimicrobial peptides from the innate immune system represent one promising class that offers a potential solution to the antibiotic resistance problem due to their mode of action on the microbial membranes. However, challenges associated with pharmacokinetics, bioavailability and off-target toxicity are slowing down the advancement and use of innate defensive peptides. Improving the therapeutic properties of these peptides is a strategy for reducing the clinical limitations and synthetic mimics of antimicrobial peptides are emerging as a promising class of molecules for a variety of antimicrobial applications. These compounds can be made significantly shorter while maintaining, or even improving antimicrobial properties, and several downsized synthetic mimics are now in clinical development for a range of infectious diseases. A variety of strategies can be employed to prepare these small compounds and this review describes the different compounds developed to date by adhering to a minimum pharmacophore based on an amphiphilic balance between cationic charge and hydrophobicity. These compounds can be made as small as dipeptides, circumventing the need for large compounds with elaborate three-dimensional structures to generate simplified and potent antimicrobial mimics for a range of medical applications. This review highlight key and recent development in the field of small antimicrobial peptide mimics as a promising class of antimicrobials, illustrating just how small you can go.https://www.frontiersin.org/articles/10.3389/fimmu.2022.915368/fullantimicrobial peptidesantibioticsynthetic mimicamphiphilicclinical developmentpeptidomimetics |
| spellingShingle | Johan Svenson Natalia Molchanova Christina I. Schroeder Antimicrobial Peptide Mimics for Clinical Use: Does Size Matter? Frontiers in Immunology antimicrobial peptides antibiotic synthetic mimic amphiphilic clinical development peptidomimetics |
| title | Antimicrobial Peptide Mimics for Clinical Use: Does Size Matter? |
| title_full | Antimicrobial Peptide Mimics for Clinical Use: Does Size Matter? |
| title_fullStr | Antimicrobial Peptide Mimics for Clinical Use: Does Size Matter? |
| title_full_unstemmed | Antimicrobial Peptide Mimics for Clinical Use: Does Size Matter? |
| title_short | Antimicrobial Peptide Mimics for Clinical Use: Does Size Matter? |
| title_sort | antimicrobial peptide mimics for clinical use does size matter |
| topic | antimicrobial peptides antibiotic synthetic mimic amphiphilic clinical development peptidomimetics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.915368/full |
| work_keys_str_mv | AT johansvenson antimicrobialpeptidemimicsforclinicalusedoessizematter AT nataliamolchanova antimicrobialpeptidemimicsforclinicalusedoessizematter AT christinaischroeder antimicrobialpeptidemimicsforclinicalusedoessizematter |