Structural characterization and biological activity of Crabrolin peptide isoforms with different positive charge

Aschi, Massimiliano; Perini, Nicoletta; Bouchemal, Nadia; Luzi, Carla; Savarin, Philippe; Bozzi, Argante; Sette, Marco

doi:10.1016/j.bbamem.2019.183055

Cited by 13 publications

(14 citation statements)

References 58 publications

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“…Molecular dynamics simulations are frequently used to provide information regarding (1) peptide conformation (e.g., % of helicity) [786][787][788][789][790][791][792][793][794][795][796][797][798], (2) peptide location (at the membrane interface or inserted into the bilayer core), and (3) orientation in the membrane [783,[787][788][789][790][792][793][794]796,[799][800][801][802][803][804][805][806]. As we stated previously, simulations can also provide information regarding the effects of the peptides on membrane properties, including (1) the extent of ordering in the acyl tails, (2) the overall membrane thickness, and (3) curvature [793,794,799,800,807] as well as the formation of membrane defects [794].…”

Section: A Clear Case Of Drug Membrane Interaction As Mechanism Of Action-antimicrobial Agentsmentioning

confidence: 99%

“…As we stated previously, simulations can also provide information regarding the effects of the peptides on membrane properties, including (1) the extent of ordering in the acyl tails, (2) the overall membrane thickness, and (3) curvature [793,794,799,800,807] as well as the formation of membrane defects [794]. MD simulations and other computational methods, combined with complementary experimental methods, can be used to design more effective antimicrobial [783,798,[808][809][810][811] and anticancer peptides [747,789,[812][813][814]. For designing new peptides, an understanding of the interactions between peptides and lipids is of particular interest.…”

Section: A Clear Case Of Drug Membrane Interaction As Mechanism Of Action-antimicrobial Agentsmentioning

confidence: 99%

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Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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Section: A Clear Case Of Drug Membrane Interaction As Mechanism Of Action-antimicrobial Agentsmentioning

confidence: 99%

Section: A Clear Case Of Drug Membrane Interaction As Mechanism Of Action-antimicrobial Agentsmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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“…Another example of venom peptides with antimicrobial activity is the 13 amino acid long crabrolin, originally described in the venom of the European hornet Vespa crabro and classified as a chemotactic factor. Its activity against selected bacteria is determined by the presence of hydrophobic groups and the positive charge, while the α-helical conformation is necessary to maintain hemolytic activity [ 231 , 232 ].…”

Section: Amps In Insect Venomsmentioning

confidence: 99%

Unraveling the Role of Antimicrobial Peptides in Insects

Stączek

Cytryńska

Zdybicka-Barabas

2023

IJMS

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Antimicrobial peptides (AMPs) are short, mainly positively charged, amphipathic molecules. AMPs are important effectors of the immune response in insects with a broad spectrum of antibacterial, antifungal, and antiparasitic activity. In addition to these well-known roles, AMPs exhibit many other, often unobvious, functions in the host. They support insects in the elimination of viral infections. AMPs participate in the regulation of brain-controlled processes, e.g., sleep and non-associative learning. By influencing neuronal health, communication, and activity, they can affect the functioning of the insect nervous system. Expansion of the AMP repertoire and loss of their specificity is connected with the aging process and lifespan of insects. Moreover, AMPs take part in maintaining gut homeostasis, regulating the number of endosymbionts as well as reducing the number of foreign microbiota. In turn, the presence of AMPs in insect venom prevents the spread of infection in social insects, where the prey may be a source of pathogens.

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“…We previously studied an antimicrobial peptide, named crabrolin, obtained from Vespa crabro [ 13 ]. This peptide is 13 amino acids long (FLPLILRKIVTAL-NH 2 ), has a net positive charge of +2 at neutral pH, and shows little antimicrobial activity [ 14 ]. In amphiphilic solvents that mimic lipid membranes, it assumes an amphipathic helical conformation [ 15 ] as well as many other AMPs.…”

Section: Introductionmentioning

confidence: 99%

“…In amphiphilic solvents that mimic lipid membranes, it assumes an amphipathic helical conformation [ 15 ] as well as many other AMPs. Replacement of some neutral amino acids with positively charged ones (FLPKILRKIVRAL-NH 2 ; crabrolin Plus) improves antimicrobial activity, maintaining the amphipathic helical propensity of the peptide, whereas a peptide in which the charge is diminished (FLPLILFWIVTAL-NH 2 ; crabrolin Minus) displays no activity [ 14 ]. Furthermore, crabrolin Plus, in contrast to the wild-type peptide, binds to isolated lipopolysaccharide, altering its micellar state [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Structural and Functional Characterization of the Newly Designed Antimicrobial Peptide Crabrolin21

et al. 2023

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(1) Background: antimicrobial resistance is becoming a dramatic problem for public health, and the design of new antimicrobial agents is an active research area. (2) Methods: based on our previous work, we designed an improved version of the crabrolin peptide and characterized its functional and structural properties with a wide range of techniques. (3) Results: the newly designed peptide, crabrolin21, is much more active than the previous ones and shows specific selectivity towards bacterial cells. (4) Conclusions: crabrolin21 shows interesting properties and deserves further studies.

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Structural characterization and biological activity of Crabrolin peptide isoforms with different positive charge

Cited by 13 publications

References 58 publications

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Unraveling the Role of Antimicrobial Peptides in Insects

Structural and Functional Characterization of the Newly Designed Antimicrobial Peptide Crabrolin21

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