Glycosylation and Lipidation Strategies: Approaches for Improving Antimicrobial Peptide Efficacy
Antimicrobial peptides (AMPs) have recently gained attention as a viable solution for combatting antibiotic resistance due to their numerous advantages, including their broad-spectrum activity, low propensity for inducing resistance, and low cytotoxicity. Unfortunately, their clinical application is...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/3/439 |
| _version_ | 1797609562994376704 |
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| author | Rosa Bellavita Simone Braccia Stefania Galdiero Annarita Falanga |
| author_facet | Rosa Bellavita Simone Braccia Stefania Galdiero Annarita Falanga |
| author_sort | Rosa Bellavita |
| collection | DOAJ |
| description | Antimicrobial peptides (AMPs) have recently gained attention as a viable solution for combatting antibiotic resistance due to their numerous advantages, including their broad-spectrum activity, low propensity for inducing resistance, and low cytotoxicity. Unfortunately, their clinical application is limited due to their short half-life and susceptibility to proteolytic cleavage by serum proteases. Indeed, several chemical strategies, such as peptide cyclization, <i>N-</i>methylation, PEGylation, glycosylation, and lipidation, are widely used for overcoming these issues. This review describes how lipidation and glycosylation are commonly used to increase AMPs’ efficacy and engineer novel AMP-based delivery systems. The glycosylation of AMPs, which involves the conjugation of sugar moieties such as glucose and <i>N-</i>acetyl galactosamine, modulates their pharmacokinetic and pharmacodynamic properties, improves their antimicrobial activity, and reduces their interaction with mammalian cells, thereby increasing selectivity toward bacterial membranes. In the same way, lipidation of AMPs, which involves the covalent addition of fatty acids, has a significant impact on their therapeutic index by influencing their physicochemical properties and interaction with bacterial and mammalian membranes. This review highlights the possibility of using glycosylation and lipidation strategies to increase the efficacy and activity of conventional AMPs. |
| first_indexed | 2024-03-11T06:02:07Z |
| format | Article |
| id | doaj.art-5734553a75f747348590d8ce437d2f8e |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T06:02:07Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-5734553a75f747348590d8ce437d2f8e2023-11-17T13:12:51ZengMDPI AGPharmaceuticals1424-82472023-03-0116343910.3390/ph16030439Glycosylation and Lipidation Strategies: Approaches for Improving Antimicrobial Peptide EfficacyRosa Bellavita0Simone Braccia1Stefania Galdiero2Annarita Falanga3Department of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Via Domenico Montesano 49, 80131 Naples, ItalyDepartment of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Via Domenico Montesano 49, 80131 Naples, ItalyDepartment of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Via Domenico Montesano 49, 80131 Naples, ItalyDepartment of Agricultural Sciences, University of Naples ‘Federico II’, Via dell’ Università 100, 80055 Portici, ItalyAntimicrobial peptides (AMPs) have recently gained attention as a viable solution for combatting antibiotic resistance due to their numerous advantages, including their broad-spectrum activity, low propensity for inducing resistance, and low cytotoxicity. Unfortunately, their clinical application is limited due to their short half-life and susceptibility to proteolytic cleavage by serum proteases. Indeed, several chemical strategies, such as peptide cyclization, <i>N-</i>methylation, PEGylation, glycosylation, and lipidation, are widely used for overcoming these issues. This review describes how lipidation and glycosylation are commonly used to increase AMPs’ efficacy and engineer novel AMP-based delivery systems. The glycosylation of AMPs, which involves the conjugation of sugar moieties such as glucose and <i>N-</i>acetyl galactosamine, modulates their pharmacokinetic and pharmacodynamic properties, improves their antimicrobial activity, and reduces their interaction with mammalian cells, thereby increasing selectivity toward bacterial membranes. In the same way, lipidation of AMPs, which involves the covalent addition of fatty acids, has a significant impact on their therapeutic index by influencing their physicochemical properties and interaction with bacterial and mammalian membranes. This review highlights the possibility of using glycosylation and lipidation strategies to increase the efficacy and activity of conventional AMPs.https://www.mdpi.com/1424-8247/16/3/439antimicrobial peptideschemical strategiesglycosylationlipidation |
| spellingShingle | Rosa Bellavita Simone Braccia Stefania Galdiero Annarita Falanga Glycosylation and Lipidation Strategies: Approaches for Improving Antimicrobial Peptide Efficacy Pharmaceuticals antimicrobial peptides chemical strategies glycosylation lipidation |
| title | Glycosylation and Lipidation Strategies: Approaches for Improving Antimicrobial Peptide Efficacy |
| title_full | Glycosylation and Lipidation Strategies: Approaches for Improving Antimicrobial Peptide Efficacy |
| title_fullStr | Glycosylation and Lipidation Strategies: Approaches for Improving Antimicrobial Peptide Efficacy |
| title_full_unstemmed | Glycosylation and Lipidation Strategies: Approaches for Improving Antimicrobial Peptide Efficacy |
| title_short | Glycosylation and Lipidation Strategies: Approaches for Improving Antimicrobial Peptide Efficacy |
| title_sort | glycosylation and lipidation strategies approaches for improving antimicrobial peptide efficacy |
| topic | antimicrobial peptides chemical strategies glycosylation lipidation |
| url | https://www.mdpi.com/1424-8247/16/3/439 |
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