(Re)Defining the Proline-Rich Antimicrobial Peptide Family and the Identification of Putative New Members

Welch, Nicholas G.; Li, Wenyi; Hossain, Mohammed Akhter; Separovic, Frances; O'Brien-Simpson, Neil M; Wade, John D.

doi:10.3389/fchem.2020.607769

Cited by 33 publications

(39 citation statements)

References 62 publications

(93 reference statements)

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“…Other key criteria of AMPs that should always be studied in detail when considering these molecules for use in clinical settings are immunogenicity and pharmacodynamics/pharmacodynamics properties. Proline-rich AMPs (PrAMPs) are a class of membrane-permeable AMPs that have been identified more than 20 years ago in mammals and insects; they have an intracellular mode of action, inhibiting protein synthesis leading to a bactericidal outcome [ 160 ]. Apidaecin Api88 (18 aa) and oncocin Onc72 (19 aa)—PrAMPs based on natural peptides isolated from milkweed bug Oncopeltus fasciatus —were shown to be nonimmunogenic in mice, unless conjugated to protein carriers, a fact attributed to the small size of these molecules [ 161 ].…”

Section: Amps—goods Vs Bads and The Long Way Towards Clinical Applicationmentioning

confidence: 99%

Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

Vanzolini

Bruschi

Rinaldi

et al. 2022

IJMS

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Despite the great strides in healthcare during the last century, some challenges still remained unanswered. The development of multi-drug resistant bacteria, the alarming growth of fungal infections, the emerging/re-emerging of viral diseases are yet a worldwide threat. Since the discovery of natural antimicrobial peptides able to broadly hit several pathogens, peptide-based therapeutics have been under the lenses of the researchers. This review aims to focus on synthetic peptides and elucidate their multifaceted mechanisms of action as antiviral, antibacterial and antifungal agents. Antimicrobial peptides generally affect highly preserved structures, e.g., the phospholipid membrane via pore formation or other constitutive targets like peptidoglycans in Gram-negative and Gram-positive bacteria, and glucan in the fungal cell wall. Additionally, some peptides are particularly active on biofilm destabilizing the microbial communities. They can also act intracellularly, e.g., on protein biosynthesis or DNA replication. Their intracellular properties are extended upon viral infection since peptides can influence several steps along the virus life cycle starting from viral receptor-cell interaction to the budding. Besides their mode of action, improvements in manufacturing to increase their half-life and performances are also taken into consideration together with advantages and impairments in the clinical usage. Thus far, the progress of new synthetic peptide-based approaches is making them a promising tool to counteract emerging infections.

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Section: Amps—goods Vs Bads and The Long Way Towards Clinical Applicationmentioning

confidence: 99%

Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

Vanzolini

Bruschi

Rinaldi

et al. 2022

IJMS

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“…Recently, a revised definition of the PrAMP as the class of AMP has been proposed [ 96 ]. According to the new definition PrAMP constitute peptides that satisfy the following set of criteria: have antibacterial activity; net charge >+1, proline contents >25%; key motif—PRP (indicative but not essential); have intracellular targets (for example, DnkA and/or 70S ribosome).…”

Section: Frequently Occurred Amino Acidsmentioning

confidence: 99%

Physicochemical Features and Peculiarities of Interaction of AMP with the Membrane

Pirtskhalava¹,

Vishnepolsky²,

Grigolava³

et al. 2021

Pharmaceuticals

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Antimicrobial peptides (AMPs) are anti-infectives that have the potential to be used as a novel and untapped class of biotherapeutics. Modes of action of antimicrobial peptides include interaction with the cell envelope (cell wall, outer- and inner-membrane). A comprehensive understanding of the peculiarities of interaction of antimicrobial peptides with the cell envelope is necessary to perform a rational design of new biotherapeutics, against which working out resistance is hard for microbes. In order to enable de novo design with low cost and high throughput, in silico predictive models have to be invoked. To develop an efficient predictive model, a comprehensive understanding of the sequence-to-function relationship is required. This knowledge will allow us to encode amino acid sequences expressively and to adequately choose the accurate AMP classifier. A shared protective layer of microbial cells is the inner, plasmatic membrane. The interaction of AMP with a biological membrane (native and/or artificial) has been comprehensively studied. We provide a review of mechanisms and results of interactions of AMP with the cell membrane, relying on the survey of physicochemical, aggregative, and structural features of AMPs. The potency and mechanism of AMP action are presented in terms of amino acid compositions and distributions of the polar and apolar residues along the chain, that is, in terms of the physicochemical features of peptides such as hydrophobicity, hydrophilicity, and amphiphilicity. The survey of current data highlights topics that should be taken into account to come up with a comprehensive explanation of the mechanisms of action of AMP and to uncover the physicochemical faces of peptides, essential to perform their function. Many different approaches have been used to classify AMPs, including machine learning. The survey of knowledge on sequences, structures, and modes of actions of AMP allows concluding that only possessing comprehensive information on physicochemical features of AMPs enables us to develop accurate classifiers and create effective methods of prediction. Consequently, this knowledge is necessary for the development of design tools for peptide-based antibiotics.

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“…AMPs that target the membrane or the cell wall have been analyzed in great detail [7,44,81], but several AMPs act on intracellular targets (Figure 1). Prolin-rich AMPs (PrAMPs) constitute a class of short, non-lytic peptides that are produced by plants and animals [82][83][84] (http://dramp.cpu-bioinfor.org/). Apidaecin, a PrAMP isolated from Apis mellifera [85], was…”

Section: Accepted Articlementioning

confidence: 99%

“…1). Proline‐rich AMPs (PrAMPs) constitute a class of short, nonlytic peptides that are produced by plants and animals [82–84] (http://dramp.cpu-bioinfor.org/). Apidaecin, a PrAMP isolated from Apis mellifera [85], was shown to inhibit bacterial translation by trapping release factors on the ribosome [8].…”

Section: Introductionmentioning

confidence: 99%

The largely unexplored biology of small proteins in pro‐ and eukaryotes

Steinberg

Koch

2021

The FEBS Journal

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The large abundance of small open reading frames (smORFs) in prokaryotic and eukaryotic genomes and the plethora of smORF-encoded small proteins became only apparent with the constant advancements in bioinformatics, genomic, proteomic and biochemical tools.Small proteins are typically defined as proteins of less than 50 amino acids in prokaryotes and of less than 100 amino acids in eukaryotes and their importance for cell physiology and cellular adaptation is only beginning to emerge. In contrast to antimicrobial peptides, which are secreted by prokaryotic and eukaryotic cells for combatting pathogens and competitors, small proteins act within the producing cell mainly by stabilizing protein assemblies and by modifying the activity of larger proteins. Production of small proteins is frequently linked to stress conditions or environmental changes and therefore cells seem to use small proteins as intracellular modifiers for adjusting cell metabolism to different intra-and extracellular cues. However, the size of small proteins imposes a major challenge for the cellular machinery required for protein folding and intracellular trafficking and recent data indicate that small proteins can engage distinct trafficking pathways. In the current review, we describe the diversity of small proteins in prokaryotes and eukaryotes, highlight distinct and common features and illustrate how they are handled by the protein trafficking machineries in prokaryotic and eukaryotic cells. Finally, we also discuss future topics of research on this fascinating but largely unexplored group of proteins.

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(Re)Defining the Proline-Rich Antimicrobial Peptide Family and the Identification of Putative New Members

Cited by 33 publications

References 62 publications

Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

Physicochemical Features and Peculiarities of Interaction of AMP with the Membrane

The largely unexplored biology of small proteins in pro‐ and eukaryotes

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