Dermaseptins, Multifunctional Antimicrobial Peptides: A Review of Their Pharmacology, Effectivity, Mechanism of Action, and Possible Future Directions

Bartels, Emiel Jacob Henri; Dekker, D.; Amiche, Mohamed

doi:10.3389/fphar.2019.01421

Cited by 49 publications

(65 citation statements)

References 110 publications

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“…In the bottom left corner of the figure, we observed several amphibian dermaseptins (e.g. APD00162, APD00163, APD00942, APD00943, APD00963, APD01351, APD01352-lime green circles) and a pair of piscine hepcidicins (APD01701, APD01702-forest green circles), none of these peptides were tested against human erythrocytes 57,58 . Besides, miscellaneous AMPs from that cluster, i.e.…”

Section: Resultsmentioning

confidence: 99%

Machine learning-guided discovery and design of non-hemolytic peptides

Plisson¹,

Ramírez-Sánchez²,

Martínez-Hernández³

2020

Sci Rep

106

104

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Reducing hurdles to clinical trials without compromising the therapeutic promises of peptide candidates becomes an essential step in peptide-based drug design. Machine-learning models are cost-effective and time-saving strategies used to predict biological activities from primary sequences. Their limitations lie in the diversity of peptide sequences and biological information within these models. Additional outlier detection methods are needed to set the boundaries for reliable predictions; the applicability domain. Antimicrobial peptides (AMPs) constitute an extensive library of peptides offering promising avenues against antibiotic-resistant infections. Most AMPs present in clinical trials are administrated topically due to their hemolytic toxicity. Here we developed machine learning models and outlier detection methods that ensure robust predictions for the discovery of AMPs and the design of novel peptides with reduced hemolytic activity. Our best models, gradient boosting classifiers, predicted the hemolytic nature from any peptide sequence with 95–97% accuracy. Nearly 70% of AMPs were predicted as hemolytic peptides. Applying multivariate outlier detection models, we found that 273 AMPs (~ 9%) could not be predicted reliably. Our combined approach led to the discovery of 34 high-confidence non-hemolytic natural AMPs, the de novo design of 507 non-hemolytic peptides, and the guidelines for non-hemolytic peptide design.

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Section: Resultsmentioning

confidence: 99%

Machine learning-guided discovery and design of non-hemolytic peptides

Plisson¹,

Ramírez-Sánchez²,

Martínez-Hernández³

2020

Sci Rep

106

104

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“…Dermaseptins (DRS) are polycationic peptides isolated from Phyllomedusa frogs that are effective against bacteria, parasites, protozoa, viruses, and cancer cells in vitro. The antimicrobial and anti-cancer activity involves the destruction of cell membranes through a carpet-like model based on their binding to the outer phospholipid layer which causes the pores formation and internalization between the phospholipid heads [ 106 ]. Dos Santos et al reported that dermaseptin B2 (DRS-B2) appears to be active towards the sulphated glycosaminoglycans (GAGs) present on the surface of PC3 prostate cancer cells membranes [ 107 ].…”

Section: Critical Issues Possible Solutions For Clinical Use Of Amentioning

confidence: 99%

“…Such interactions may cause greater fluidity of tumor cell surfaces and increased destabilization thus influencing the receptors link and communications between the environment and the tumor cells [ 36 ]. DRS-B1-B2, DRS-S1-S5 DRS-O1, DRS-CA1 DRS-DU1 are effective against fungi in vitro demonstrating cytotoxicity on Candida albicans cultures, with DRS-S3 triggering apopotosis [ 106 ]. The DRS-S4 and DRS-9 possess antiviral activities against HPVs, associated with genital infection and cancer, and HSV by interfering with viral and cellular factors in the early phase of viral replication.…”

Section: Critical Issues Possible Solutions For Clinical Use Of Amentioning

confidence: 99%

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Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities

et al. 2020

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Antimicrobial peptides (AMPs), or host defense peptides, are small cationic or amphipathic molecules produced by prokaryotic and eukaryotic organisms that play a key role in the innate immune defense against viruses, bacteria and fungi. AMPs have either antimicrobial or anticancer activities. Indeed, cationic AMPs are able to disrupt microbial cell membranes by interacting with negatively charged phospholipids. Moreover, several peptides are capable to trigger cytotoxicity of human cancer cells by binding to negatively charged phosphatidylserine moieties which are selectively exposed on the outer surface of cancer cell plasma membranes. In addition, some AMPs, such as LTX-315, have shown to induce release of tumor antigens and potent damage associated molecular patterns by causing alterations in the intracellular organelles of cancer cells. Given the recognized medical need of novel anticancer drugs, AMPs could represent a potential source of effective therapeutic agents, either alone or in combination with other small molecules, in oncology. In this review we summarize and describe the properties and the mode of action of AMPs as well as the strategies to increase their selectivity toward specific cancer cells.

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“…Antimicrobial peptides (AMPs) are a special class of biologically active peptides [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. They are important because of their antimicrobial effects on various pathogens, including drug-resistant bacteria, fungi, viruses, and parasites.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic Analysis of 1000 Amphibian Antimicrobial Peptides Uncovers Multiple Length-Dependent Correlations for Peptide Design and Prediction

Wang

2020

Antibiotics

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Amphibians are widely distributed on different continents, except for the polar regions. They are important sources for the isolation, purification and characterization of natural compounds, including peptides with various functions. Innate immune antimicrobial peptides (AMPs) play a critical role in warding off invading pathogens, such as bacteria, fungi, parasites, and viruses. They may also have other biological functions such as endotoxin neutralization, chemotaxis, anti-inflammation, and wound healing. This article documents a bioinformatic analysis of over 1000 amphibian antimicrobial peptides registered in the Antimicrobial Peptide Database (APD) in the past 18 years. These anuran peptides were discovered in Africa, Asia, Australia, Europe, and America from 1985 to 2019. Genomic and peptidomic studies accelerated the discovery pace and underscored the necessity in establishing criteria for peptide entry into the APD. A total of 99.9% of the anuran antimicrobial peptides are less than 50 amino acids with an average length of 24 and a net charge of +2.5. Interestingly, the various amphibian peptide families (e.g., temporins, brevinins, esculentins) can be connected through multiple length-dependent relationships. With an increase in length, peptide net charge increases, while the hydrophobic content decreases. In addition, glycine, leucine, lysine, and proline all show linear correlations with peptide length. These correlations improve our understanding of amphibian peptides and may be useful for prediction and design of new linear peptides with potential applications in treating infectious diseases, cancer and diabetes.

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Dermaseptins, Multifunctional Antimicrobial Peptides: A Review of Their Pharmacology, Effectivity, Mechanism of Action, and Possible Future Directions

Cited by 49 publications

References 110 publications

Machine learning-guided discovery and design of non-hemolytic peptides

Machine learning-guided discovery and design of non-hemolytic peptides

Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities

Bioinformatic Analysis of 1000 Amphibian Antimicrobial Peptides Uncovers Multiple Length-Dependent Correlations for Peptide Design and Prediction

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