Structure-Activity Relationships of Insect Defensins

Koehbach, Johannes

doi:10.3389/fchem.2017.00045

Cited by 57 publications

(52 citation statements)

References 104 publications

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“…However, their use as therapeutic lead molecules is challenged by their typically poor stability and lack of oral bioavailability. This is often due to the linear nature of peptides that not only exhibit free ends but multiple cleavage sites that are readily recognized by enzymes that degrade peptide chains into inactive fragments or single amino acids [1][2][3][4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Conceptual DFT as a Helpful Chemoinformatics Tool for the Study of the Clavanin Family of Antimicrobial Marine Peptides

Flores-Holgúın¹,

Frau²,

Glossman‐Mitnik³

2021

Density Functional Theory Calculations

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A well-behaved model chemistry previously validated for the study of the chemical reactivity of peptides was considered for the calculation of the molecular properties and structures of the clavanin family of antimicrobial marine peptides. A methodology based on conceptual density functional theory (CDFT) was chosen for the determination of the reactivity descriptors. The molecular active sites were associated with the active regions of the molecules related to the nucleophilic and electrophilic Fukui functions. Finally, the drug-likenesses and the bioactivity scores for the clavanin peptides were predicted through a homology methodology relating them with the calculated reactivity descriptors, while other properties like the pKas were determined following a methodology developed by our group.

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Section: Introductionmentioning

confidence: 99%

Conceptual DFT as a Helpful Chemoinformatics Tool for the Study of the Clavanin Family of Antimicrobial Marine Peptides

Flores-Holgúın¹,

Frau²,

Glossman‐Mitnik³

2021

Density Functional Theory Calculations

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“…The mechanism of action of housefly CECROPIN is thought to mainly damage the bacteria membrane, which could lead to the leakage of cytoplasmic contents (Lu et al, 2012). DEFENSINS can cause bacteria membrane lysis (Koehbach, 2017), and ATTACIN was found to inhibit outer membrane synthesis (Carlsson, Nyström, de Cock, & Bennich, 1998). Compared to individual AMP, except the membrane targeting mechanism, Md-AMPs also has a nonmembrane targeting mechanism, which may be due to the synergistic interactions of multiple AMPs.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial peptides from the edible insect Musca domestica and their preservation effect on chilled pork

Dang

Zheng

Wang

et al. 2019

J Food Process Preserv

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Antimicrobial compounds from natural sources are a promising alternative to address the consumer demand of food without chemical additives. In this study, antimicrobial peptides (AMPs) from infected Musca domestica pupae (Md‐AMPs) bred under clean conditions were isolated and prepared on a large scale. In these Md‐AMPs, seven AMPs families were identified by liquid chromatography–tandem mass spectrometry. Md‐AMPs at concentrations from 0.4 to 0.8 mg/ml exhibited antibacterial activity and showed negligible hemolytic activity against human erythrocytes. Md‐AMPs increased bacterial membrane permeability of four tested strains, resulting in the leakage of phosphorus‐containing materials and Ca2+. Md‐AMPs bound plasmid DNA and inhibited its migration in a concentration‐dependent manner. Treatment with Md‐AMPs alone or in combination with nisin, and ethylenediaminetetraacetic acid was efficient in inhibiting bacterial growth in chilled pork and extended the shelf life up to 6 days. Practical applications Insects have been widely used as foods and many biofunctional components are found in insects. In this work, we isolated and prepared AMPs from M. domestica, and its antibacterial activity, hemolytic activity, and mechanism of action were investigated. Trials in real food products showed that Md‐AMPs alone or a combination of three natural antimicrobials could remarkably inhibit bacterial growth in chilled pork. These results suggest that Md‐AMPs can be used as food preservatives.

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“…peptides with two disulfide bonds linking the same α-helix with the same terminal β-strand in a parallel arrangement. Cis-defensins where the third disulfide bond connects the N-terminal loop with the second β-sheet are known as cysteine-stabilized αβ defensins (CSαβ) [35].…”

Section: Peptides With α-And βStructural Elementsmentioning

confidence: 99%

The Vast Structural Diversity of Antimicrobial Peptides

Koehbach

Craik

2019

Trends in Pharmacological Sciences

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181

133

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Antimicrobial peptides (AMPs) occur in all kingdoms of life and are integral to host defense. They have diverse structures and target a variety of organisms, both by non-specific membrane interactions or via specific targets. Here we discuss the structures of AMPs from the four main classes currently recognized, i.e. peptides with (i) α-helical; (ii) β-sheet; (iii) αβ; and (iv) non-αβ elements as well as the growing pool of complex topologies including various post-translational modifications. We propose to group these latter peptides into a fifth class of AMPs. Such peptides exhibit high stability and amenability to chemical engineering, making them of interest for the development of novel antimicrobial agents. Advances and challenges in the development of these peptides towards therapeutic leads are presented. AMPsa diverse, but unifying strategy for defense Antimicrobial resistance has been identified as a major threat to public health and without immediate and global action the world is headed for a dangerous post-antibiotic era [1]. Thus, there is an urgent need for the development of novel antibiotic drugs to treat infectious diseases. In contrast to the rising numbers of multi drug resistant pathogens the rate of discovery of novel drug candidates is dwindling [2]. In this regard antimicrobial peptides (AMP) are a promising class of bioactive compounds that have attracted increasing attention over recent years. Their broad spectrum of activities extends beyond the killing of bacteria and fungi, with several AMPs also exhibiting antiviral [3], antiparasitic [4] or anticancer activities [5]. Furthermore, their multifaceted mechanisms-of-action potentially reduce their susceptibility to suffer from microbial resistance [6]. Starting in the 1980s, at a time when the numbers of novel antibacterial agents started to drop, the field of AMP research gained momentum when several novel examples were independently discovered across different species. These included peptides such as the cecropins from insects [7], the magainins from amphibians [8] and the mammalian defensins [9] to name a few. Since then a plethora of AMPs has been identified from all kingdoms of life, from bacteria to fungi to plants and animals. It is not only evident that these peptides play an integral part of an organism's innate defense machinery, but their variety also makes them a rich source for the discovery of potential novel drug leads. Their distribution among virtually all living organisms is complemented by their structural variety and range of antimicrobial activities. In this review we highlight this vast structural diversity of antimicrobial peptides. As well as providing a brief overview of the structures of well-known classes of AMPs, we introduce the growing class of structurally complex AMP topologies, in particular, cyclic and cysteine-rich defense peptides. We discuss recent progress and challenges in the characterization and development of peptide-based antibacterial molecules. 3 Structural classes of antimicrobial peptides Th...

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Structure-Activity Relationships of Insect Defensins

Cited by 57 publications

References 104 publications

Conceptual DFT as a Helpful Chemoinformatics Tool for the Study of the Clavanin Family of Antimicrobial Marine Peptides

Conceptual DFT as a Helpful Chemoinformatics Tool for the Study of the Clavanin Family of Antimicrobial Marine Peptides

Antimicrobial peptides from the edible insect Musca domestica and their preservation effect on chilled pork

The Vast Structural Diversity of Antimicrobial Peptides

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