Pub Date : 2022-01-01Epub Date: 2021-10-11DOI: 10.1002/pep2.24245
Achyut Dahal, Jafrin Jobayer Sonju, Konstantin G Kousoulas, Seetharama D Jois
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Covid-19 pandemic has caused high morbidity and mortality rates worldwide. Virus entry into cells can be blocked using several strategies, including inhibition of protein-protein interactions (PPIs) between the viral spike glycoprotein and cellular receptors, as well as blocking of spike protein conformational changes that are required for cleavage/activation and fusogenicity. The spike-mediated viral attachment and entry into cells via fusion of the viral envelope with cellular membranes involve PPIs mediated by short peptide fragments exhibiting particular secondary structures. Thus, peptides that can inhibit these PPIs may be used as potential antiviral agents preventing virus entry and spread. This review is focused on peptides and peptidomimetics as PPI modulators and protease inhibitors against SARS-CoV-2.
严重急性呼吸系统综合征冠状病毒-2（SARS-CoV-2）Covid-19大流行在全球范围内造成了很高的发病率和死亡率。可采用多种策略阻止病毒进入细胞，包括抑制病毒尖峰糖蛋白与细胞受体之间的蛋白-蛋白相互作用（PPIs），以及阻止尖峰蛋白构象变化（裂解/活化和融合所需的构象变化）。尖峰蛋白介导的病毒附着和通过病毒包膜与细胞膜融合进入细胞的过程涉及由表现出特殊二级结构的短肽片段介导的 PPI。因此，能够抑制这些 PPIs 的多肽可用作潜在的抗病毒药物，防止病毒进入和传播。这篇综述主要介绍了作为 PPI 调节剂和蛋白酶抑制剂的肽类和拟肽类药物对 SARS-CoV-2 的作用。
{"title":"Peptides and peptidomimetics as therapeutic agents for Covid-19.","authors":"Achyut Dahal, Jafrin Jobayer Sonju, Konstantin G Kousoulas, Seetharama D Jois","doi":"10.1002/pep2.24245","DOIUrl":"10.1002/pep2.24245","url":null,"abstract":"<p><p>The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Covid-19 pandemic has caused high morbidity and mortality rates worldwide. Virus entry into cells can be blocked using several strategies, including inhibition of protein-protein interactions (PPIs) between the viral spike glycoprotein and cellular receptors, as well as blocking of spike protein conformational changes that are required for cleavage/activation and fusogenicity. The spike-mediated viral attachment and entry into cells via fusion of the viral envelope with cellular membranes involve PPIs mediated by short peptide fragments exhibiting particular secondary structures. Thus, peptides that can inhibit these PPIs may be used as potential antiviral agents preventing virus entry and spread. This review is focused on peptides and peptidomimetics as PPI modulators and protease inhibitors against SARS-CoV-2.</p>","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"114 1","pages":"e24245"},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8646791/pdf/PEP2-114-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10594771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Choudhury, A. Maity, S. Chakraborty, R. Chakrabarti
Since its first detection in 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has been the cause of millions of deaths worldwide. Despite the development and administration of different vaccines, the situation is still worrisome as the virus is constantly mutating to produce newer variants some of which are highly infectious. This raises an urgent requirement to understand the infection mechanism and thereby design therapeutic‐based treatment for COVID‐19. The gateway of the virus to the host cell is mediated by the binding of the receptor binding domain (RBD) of the virus spike protein to the angiotensin‐converting enzyme 2 (ACE2) of the human cell. Therefore, the RBD of SARS‐CoV‐2 can be used as a target to design therapeutics. The α1 helix of ACE2, which forms direct contact with the RBD surface, has been used as a template in the current study to design stapled peptide therapeutics. Using computer simulation, the mechanism and thermodynamics of the binding of six stapled peptides with RBD have been estimated. Among these, the one with two lactam stapling agents has shown binding affinity, sufficient to overcome RBD‐ACE2 binding. Analyses of the mechanistic detail reveal that a reorganization of amino acids at the RBD‐ACE2 interface produces favorable enthalpy of binding whereas conformational restriction of the free peptide reduces the loss in entropy to result higher binding affinity. The understanding of the relation of the nature of the stapling agent with their binding affinity opens up the avenue to explore stapled peptides as therapeutic against SARS‐CoV‐2.
{"title":"Computational design of stapled peptide inhibitor against SARS‐CoV‐2 receptor binding domain","authors":"A. Choudhury, A. Maity, S. Chakraborty, R. Chakrabarti","doi":"10.1002/pep2.24267","DOIUrl":"https://doi.org/10.1002/pep2.24267","url":null,"abstract":"Since its first detection in 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has been the cause of millions of deaths worldwide. Despite the development and administration of different vaccines, the situation is still worrisome as the virus is constantly mutating to produce newer variants some of which are highly infectious. This raises an urgent requirement to understand the infection mechanism and thereby design therapeutic‐based treatment for COVID‐19. The gateway of the virus to the host cell is mediated by the binding of the receptor binding domain (RBD) of the virus spike protein to the angiotensin‐converting enzyme 2 (ACE2) of the human cell. Therefore, the RBD of SARS‐CoV‐2 can be used as a target to design therapeutics. The α1 helix of ACE2, which forms direct contact with the RBD surface, has been used as a template in the current study to design stapled peptide therapeutics. Using computer simulation, the mechanism and thermodynamics of the binding of six stapled peptides with RBD have been estimated. Among these, the one with two lactam stapling agents has shown binding affinity, sufficient to overcome RBD‐ACE2 binding. Analyses of the mechanistic detail reveal that a reorganization of amino acids at the RBD‐ACE2 interface produces favorable enthalpy of binding whereas conformational restriction of the free peptide reduces the loss in entropy to result higher binding affinity. The understanding of the relation of the nature of the stapling agent with their binding affinity opens up the avenue to explore stapled peptides as therapeutic against SARS‐CoV‐2.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"113 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80623589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kousuke Mihara, Natsumi Nakajima, I. Fujii, Daisuke Fujiwara
Conformationally constrained peptides are attracting attention as peptide‐based molecular tools in chemical biology and drug discovery because of their desirable properties such as high selectivity for target binding and stability toward proteolytic enzymes. We previously reported a protein kinase–focused helix‐loop‐helix (HLH) peptide library. The library was constructed by phage display and subsequent chemical modification with adenosine that was employed as an anchor molecule binding to the ATP‐binding pocket of kinase. Here, we discovered and characterized HLH peptides that bind to and inhibit the serine/threonine protein kinase IKKε, a member of the IκB kinase (IKK) family. Screening the library against IKKε identified de novo HLH peptides binding to the kinase. One of the peptides, IKK‐05, showed a high α‐helical content and inhibited IKKε with a mixed‐inhibition mechanism with respect to ATP. The adenosine‐tethering peptide Adc‐IKK‐05 demonstrated significantly enhanced enzyme inhibition activity, indicating a bivalency effect in binding to IKKε. In addition, Adc‐IKK‐05 showed the highest inhibitory activity against IKKε of the IKK family members and other families tested. The peptides obtained in this research can be developed as molecular tools to study the biological functions of IKKε and to obtain structural insights for the design of selective IKKε inhibitors.
{"title":"Generation of inhibitory peptides for IKKε from a kinase‐focused phage library of helix‐loop‐helix peptides","authors":"Kousuke Mihara, Natsumi Nakajima, I. Fujii, Daisuke Fujiwara","doi":"10.1002/pep2.24253","DOIUrl":"https://doi.org/10.1002/pep2.24253","url":null,"abstract":"Conformationally constrained peptides are attracting attention as peptide‐based molecular tools in chemical biology and drug discovery because of their desirable properties such as high selectivity for target binding and stability toward proteolytic enzymes. We previously reported a protein kinase–focused helix‐loop‐helix (HLH) peptide library. The library was constructed by phage display and subsequent chemical modification with adenosine that was employed as an anchor molecule binding to the ATP‐binding pocket of kinase. Here, we discovered and characterized HLH peptides that bind to and inhibit the serine/threonine protein kinase IKKε, a member of the IκB kinase (IKK) family. Screening the library against IKKε identified de novo HLH peptides binding to the kinase. One of the peptides, IKK‐05, showed a high α‐helical content and inhibited IKKε with a mixed‐inhibition mechanism with respect to ATP. The adenosine‐tethering peptide Adc‐IKK‐05 demonstrated significantly enhanced enzyme inhibition activity, indicating a bivalency effect in binding to IKKε. In addition, Adc‐IKK‐05 showed the highest inhibitory activity against IKKε of the IKK family members and other families tested. The peptides obtained in this research can be developed as molecular tools to study the biological functions of IKKε and to obtain structural insights for the design of selective IKKε inhibitors.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46074409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amylin is a 37‐residue peptide hormone, which is co‐secreted with insulin and prevents postprandial spikes in blood glycemia by slowing gastric emptying and promoting satiety. Amylin is prone to aggregate into oligomers and amyloid fibrils, which is related to the onset of type 2 diabetes, and hampers its use as a biopharmaceutical. To overcome the instability and extend its in vivo half‐life it has been proposed the conjugation of amylin with polyethylene glycol (PEG) at the HNζ or the HNα amines of Lys1. Here we used two‐dimensional nuclear magnetic resonance spectra aiming the unambiguous identification of the site of covalent modification on amylin. The coupling of PEG causes both a substantial decrease in the chemical exchange of their HN and alterations in the chemical shifts at both the HN and the neighborhood hydrocarbon groups including CHα, CHδ and CHε of Lys1. Additional analysis of chemical shifts indicates alteration in the HNα solvent accessibility of residues Cys2, Asn3, Ala5, Cys7, and Gln10, and confirmed the presence of oxidized Cys2 and Cys7. We believe that the methodology described here is a reference for the characterization of chemical coupling of a number of biopharmaceuticals.
{"title":"Unambiguous characterization of PEGylation site on human amylin by two‐dimensional nuclear magnetic resonance spectroscopy","authors":"L. M. T. Lima, T. S. Araújo, M. Almeida","doi":"10.1002/pep2.24252","DOIUrl":"https://doi.org/10.1002/pep2.24252","url":null,"abstract":"Amylin is a 37‐residue peptide hormone, which is co‐secreted with insulin and prevents postprandial spikes in blood glycemia by slowing gastric emptying and promoting satiety. Amylin is prone to aggregate into oligomers and amyloid fibrils, which is related to the onset of type 2 diabetes, and hampers its use as a biopharmaceutical. To overcome the instability and extend its in vivo half‐life it has been proposed the conjugation of amylin with polyethylene glycol (PEG) at the HNζ or the HNα amines of Lys1. Here we used two‐dimensional nuclear magnetic resonance spectra aiming the unambiguous identification of the site of covalent modification on amylin. The coupling of PEG causes both a substantial decrease in the chemical exchange of their HN and alterations in the chemical shifts at both the HN and the neighborhood hydrocarbon groups including CHα, CHδ and CHε of Lys1. Additional analysis of chemical shifts indicates alteration in the HNα solvent accessibility of residues Cys2, Asn3, Ala5, Cys7, and Gln10, and confirmed the presence of oxidized Cys2 and Cys7. We believe that the methodology described here is a reference for the characterization of chemical coupling of a number of biopharmaceuticals.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48293618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leah G. Helton, H. Rideout, F. Herberg, E. Kennedy
Leucine rich repeat kinase 2 (LRRK2) is the most common genetic contributor to Parkinson's disease (PD), a complex neurodegenerative disorder affecting nearly 10 million people worldwide. Pathogenic mutations within LRRK2 often induce increased kinase activity, an effect that can be abolished with many small molecule inhibitors; however, these small molecule inhibitors are currently limited by their toxicities. Given the large and complex nature of LRRK2, more recent efforts have focused on protein–protein interactions (PPIs) involving LRRK2 and how they can contribute to PD. Here, we review recently resolved structures of LRRK2 and highlight unique interfaces driving both catalytic and non‐catalytic activities. Combining new structural information with established in vitro and in vivo data clarifies the role of PPIs in driving LRRK2‐mediated disease pathogenesis. Since constrained peptides and peptidomimetics have the potential to engage with elongated, hydrophobic interfaces that were previously considered “undruggable,” they may provide a unique handle for LRRK2 targeting. Here, we discuss the use of constrained peptides and peptidomimetics to target LRRK2 as a strategy to downregulate its pathological activity.
{"title":"Leucine rich repeat kinase 2 (LRRK2) peptide modulators: Recent advances and future directions","authors":"Leah G. Helton, H. Rideout, F. Herberg, E. Kennedy","doi":"10.1002/pep2.24251","DOIUrl":"https://doi.org/10.1002/pep2.24251","url":null,"abstract":"Leucine rich repeat kinase 2 (LRRK2) is the most common genetic contributor to Parkinson's disease (PD), a complex neurodegenerative disorder affecting nearly 10 million people worldwide. Pathogenic mutations within LRRK2 often induce increased kinase activity, an effect that can be abolished with many small molecule inhibitors; however, these small molecule inhibitors are currently limited by their toxicities. Given the large and complex nature of LRRK2, more recent efforts have focused on protein–protein interactions (PPIs) involving LRRK2 and how they can contribute to PD. Here, we review recently resolved structures of LRRK2 and highlight unique interfaces driving both catalytic and non‐catalytic activities. Combining new structural information with established in vitro and in vivo data clarifies the role of PPIs in driving LRRK2‐mediated disease pathogenesis. Since constrained peptides and peptidomimetics have the potential to engage with elongated, hydrophobic interfaces that were previously considered “undruggable,” they may provide a unique handle for LRRK2 targeting. Here, we discuss the use of constrained peptides and peptidomimetics to target LRRK2 as a strategy to downregulate its pathological activity.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44970207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Clark, Thanh Huyen Phan, A. Song, A. Ouellette, A. C. Conibear, K. Rosengren
Defensins are key components of both innate and adaptive immune responses to pathogens. Cryptdins are mouse alpha‐defensins that are secreted from Paneth cells in the small intestine and have disulfide‐stabilised structures and antibacterial activities against both Gram‐positive and Gram‐negative bacteria. The folding and three‐dimensional structures of alpha‐defensins are thought to depend on a conserved glycine residue that forms a β‐bulge. Here we investigated the role of this conserved glycine at position 19 of cryptdin‐4 (Crp4) in terms of the folding, structure and stability. A Crp4 variant with D‐Ala at position 19 folded efficiently, was stabilised by a large number of hydrogen bonds, and resisted proteolysis in simulated intestinal fluid. Although a variant with L‐Ala at position 19 was able to adopt the correct fold, it showed less efficient folding and was degraded more rapidly than the D‐Ala variant. These results demonstrate the key role that glycine residues can have in folding of bioactive peptides and can provide insights to guide design of stable antimicrobial peptides that fold efficiently.
{"title":"A conserved β‐bulge glycine residue facilitates folding and increases stability of the mouse α‐defensin cryptdin‐4","authors":"R. Clark, Thanh Huyen Phan, A. Song, A. Ouellette, A. C. Conibear, K. Rosengren","doi":"10.1002/pep2.24250","DOIUrl":"https://doi.org/10.1002/pep2.24250","url":null,"abstract":"Defensins are key components of both innate and adaptive immune responses to pathogens. Cryptdins are mouse alpha‐defensins that are secreted from Paneth cells in the small intestine and have disulfide‐stabilised structures and antibacterial activities against both Gram‐positive and Gram‐negative bacteria. The folding and three‐dimensional structures of alpha‐defensins are thought to depend on a conserved glycine residue that forms a β‐bulge. Here we investigated the role of this conserved glycine at position 19 of cryptdin‐4 (Crp4) in terms of the folding, structure and stability. A Crp4 variant with D‐Ala at position 19 folded efficiently, was stabilised by a large number of hydrogen bonds, and resisted proteolysis in simulated intestinal fluid. Although a variant with L‐Ala at position 19 was able to adopt the correct fold, it showed less efficient folding and was degraded more rapidly than the D‐Ala variant. These results demonstrate the key role that glycine residues can have in folding of bioactive peptides and can provide insights to guide design of stable antimicrobial peptides that fold efficiently.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44169021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood‐brain barrier peptides (BBPs) play a promising role in current drug study of central nervous system diseases. Hence, it is an urgent need to rapidly and accurately discriminating BBPs from non‐BBPs. Experimental approaches are the first choice, however, these methods are expensive and take a lot of time. Thus, more and more researchers focused their attention on computational models. In current work, we developed a support vector machine (SVM) based model to identify BBPs. First, amino acids physicochemical properties were employed to represent peptide sequences, and Pearson's correlation coefficient (PCC) and maximal information coefficient (MIC) were applied to extract useful information. Then, similarity network fusion algorithm was utilized to integrate these two different kinds of features. Next, Fisher algorithm was used to pick out the discriminative features. Finally, these selected features were input into SVM for distinguishing BBPs from non‐BBPs. The proposed model achieved 100.00% and 89.47% classification accuracies on training and independent datasets, respectively. Additionally, we found that pK2 (NH3) property of amino acid plays a key role in discriminating BBPs from non‐BBPs. The results showed that our proposed method is effective, and achieved a significantly improvement in identifying BBPs, as compared with the state‐of‐the‐art approach. The Matlab codes and datasets are freely available at https://figshare.com/articles/online_resource/iBBPs_zip/14723766.
{"title":"Identifying blood‐brain barrier peptides by using amino acids physicochemical properties and features fusion method","authors":"Hongliang Zou","doi":"10.1002/pep2.24247","DOIUrl":"https://doi.org/10.1002/pep2.24247","url":null,"abstract":"Blood‐brain barrier peptides (BBPs) play a promising role in current drug study of central nervous system diseases. Hence, it is an urgent need to rapidly and accurately discriminating BBPs from non‐BBPs. Experimental approaches are the first choice, however, these methods are expensive and take a lot of time. Thus, more and more researchers focused their attention on computational models. In current work, we developed a support vector machine (SVM) based model to identify BBPs. First, amino acids physicochemical properties were employed to represent peptide sequences, and Pearson's correlation coefficient (PCC) and maximal information coefficient (MIC) were applied to extract useful information. Then, similarity network fusion algorithm was utilized to integrate these two different kinds of features. Next, Fisher algorithm was used to pick out the discriminative features. Finally, these selected features were input into SVM for distinguishing BBPs from non‐BBPs. The proposed model achieved 100.00% and 89.47% classification accuracies on training and independent datasets, respectively. Additionally, we found that pK2 (NH3) property of amino acid plays a key role in discriminating BBPs from non‐BBPs. The results showed that our proposed method is effective, and achieved a significantly improvement in identifying BBPs, as compared with the state‐of‐the‐art approach. The Matlab codes and datasets are freely available at https://figshare.com/articles/online_resource/iBBPs_zip/14723766.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43903161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We need new treatment options to control bacterial infections. Bacteria use several strategies to resist drug treatment, including modification of the drug target, and adaptation to a different lifestyle, such as intracellular niches within host cells. Drugs that act on diverse targets are less likely to induce resistance in bacteria, than current antibiotics acting on a single molecular target. Antimicrobial peptides have been explored as a new class of antibiotics because they selectively kill bacteria via a mechanism that involves recognition of the negatively charged microbial surface. Furthermore, antimicrobial peptides with cell‐penetrating properties can cross host cell membranes and target bacteria in the cytosol or sequestered in vesicles. Therefore, bacteria in intracellular niches are less capable of evading treatment and the likelihood of establishing drug resistance is further reduced. This review highlights the potential of antimicrobial peptides as alternative therapeutics to target bacterial pathogens in both extracellular and intracellular environments, and to avoid acquired drug‐resistance.
{"title":"Antimicrobial peptides provide wider coverage for targeting drug‐resistant bacterial pathogens","authors":"Anna S. Amiss, S. Henriques, N. Lawrence","doi":"10.1002/pep2.24246","DOIUrl":"https://doi.org/10.1002/pep2.24246","url":null,"abstract":"We need new treatment options to control bacterial infections. Bacteria use several strategies to resist drug treatment, including modification of the drug target, and adaptation to a different lifestyle, such as intracellular niches within host cells. Drugs that act on diverse targets are less likely to induce resistance in bacteria, than current antibiotics acting on a single molecular target. Antimicrobial peptides have been explored as a new class of antibiotics because they selectively kill bacteria via a mechanism that involves recognition of the negatively charged microbial surface. Furthermore, antimicrobial peptides with cell‐penetrating properties can cross host cell membranes and target bacteria in the cytosol or sequestered in vesicles. Therefore, bacteria in intracellular niches are less capable of evading treatment and the likelihood of establishing drug resistance is further reduced. This review highlights the potential of antimicrobial peptides as alternative therapeutics to target bacterial pathogens in both extracellular and intracellular environments, and to avoid acquired drug‐resistance.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45840893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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