Evaluation of Lipopeptide (Daptomycin) Aggregation Using Fluorescence, Light Scattering, and Nuclear Magnetic Resonance Spectroscopy

Qiu, Jiang; Kirsch, Lee E.

doi:10.1002/jps.23859

Cited by 28 publications

(31 citation statements)

References 42 publications

(64 reference statements)

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“…A similar view has been presented by Qiu et al, 40 who observed the aggregation of native daptomycin by fluorescence at concentrations above 0.06 mM or 100 µg/ml in the presence of 1 mM Ca 2+ . However, such daptomycin concentrations still substantially exceed the MICs for clinically susceptible pathogens; they occur in human plasma only immediately after application of the drug; and moreover, 90% of the total amount of daptomycin in plasma is protein-bound, most likely in monomeric form, 43,44 and the unbound remainder would remain well below the experimental aggregation threshold.…”

Section: Calcium-induced Aggregation and Its Role In Daptomycin Delivsupporting

confidence: 83%

“…This question has been studied with 1 H-NMR 36,39 and optical methods. 40 In the absence of calcium and at pH 7.4 or higher, daptomycin aggregation is minimal or absent at millimolar concentrations, whereas under acidic conditions aggregates may form at concentrations as low as 0.12-0.2 mM. This pH-dependent variation can be explained by the ionization state of apo-daptomycin.…”

Section: Aggregation Of Free Daptomycin In Solutionmentioning

confidence: 99%

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The action mechanism of daptomycin

Taylor

Palmer

2016

Bioorganic & Medicinal Chemistry

220

172

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Daptomycin is a lipopeptide antibiotic produced by the soil bacterium Streptomyces roseosporus that is clinically used to treat severe infections with Grampositive bacteria. In this review, we discuss the mode of action of this important antibiotic. Although daptomycin is structurally related to amphomycin and similar lipopeptides that inhibit peptidoglycan biosynthesis, experimental studies have not produced clear evidence that daptomycin shares their action mechanism. Instead, the best characterized effect of daptomycin is the permeabilization and depolarization of the bacterial cell membrane. This activity, which can account for daptomycin's bactericidal effect, correlates with the level of phosphatidylglycerol (PG) in the membrane. Accordingly, reduced synthesis of PG or its increased conversion to lysyl-PG promotes bacterial resistance to daptomycin. While other resistance mechanisms suggest that daptomycin may indeed directly interfere with cell wall synthesis or cell division, such effects still await direct experimental confirmation. Daptomycin's complex structure and biosynthesis have hampered the analysis of its structure activity relationships. Novel methods of total synthesis, including a recent one that is carried out entirely on a solid phase, will enable a more thorough and systematic exploration of the sequence space.

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Section: Calcium-induced Aggregation and Its Role In Daptomycin Delivsupporting

confidence: 83%

Section: Aggregation Of Free Daptomycin In Solutionmentioning

confidence: 99%

The action mechanism of daptomycin

Taylor

Palmer

2016

Bioorganic & Medicinal Chemistry

220

172

View full text Add to dashboard Cite

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“…The significant fluorescence emission enhancement at 460 nm could be the self‐association aggregation of daptomycin or the interaction of daptomycin with dendrimers. However, previous studies using a variety of orthogonal analytical approaches including NMR, fluorescence, and dynamic light scattering have demonstrated that the minimum critical aggregation concentration for daptomycin in the pH range 3 to 7 was always more than 100 μM . The existing daptomycin concentration here was only 3.0 μM.…”

Section: Resultsmentioning

confidence: 65%

“…The significant fluorescence emission enhancement at 460 nm could be the self-association aggregation of daptomycin or the interaction of daptomycin with dendrimers. However, previous studies using a variety of orthogonal analytical approaches including NMR, fluorescence, and dynamic light scattering have demonstrated that the minimum critical aggregation concentration for daptomycin in the pH range 3 to 7 was always more than 100 μM [27]. The existing daptomycin ) and capacity constant (n; molecules of daptomycin per one molecule of PAMAM dendrimer) at various pH ranges of the binding interaction between daptomycin and various PAMAM dendrimer generation estimated by simultaneous fitting using WinNonlin software with fixing the molar signal coefficient (ΔE 1 and ΔE 2 ) as a constant at 240.…”

Section: Fluorescence Changes Associated With Pamam-daptomycin Bindingmentioning

confidence: 96%

The interaction mechanism between lipopeptide (daptomycin) and polyamidoamine (PAMAM) dendrimers

et al. 2015

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The interaction mechanism of lipopeptide antibiotic daptomycin and polyamidoamine (PAMAM) dendrimers was studied using fluorescence spectroscopy. The fluorescence changes observed are associated with daptomycin-dendrimer interactions. The binding isotherms were constructed by plotting the fluorescence difference at 460 nm from kynurenine (Kyn-13) of daptomycin in the presence and absence of dendrimer. A one-site and two-site binding model were quantitatively generated to estimate binding capacity and affinity constants from the isotherms. The shape of the binding isotherm and the dependence of the estimated capacity constants on dendrimer sizes and solvent pH values provide meaningful insight into the mechanism of interactions. A one-site binding model adequately describes the binding isotherm obtained under a variety of experimental conditions with dendrimers of various sizes in the optimal binding pH region 3.5 to 4.5. Comparing the pH-dependent binding capacity with the ionization profiles of daptomycin and dendrimer, the ionized aspartic acid residue (Asp-9) of daptomycin primarily interact with PAMAM cationic surface amine.

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“…At this concentration, the membrane rupture effect of LPs is evident. For example, it has been found that the antimicrobial property of daptomycin is a cooperative phenomenon above a threshold concentration [63]. Moreover, the antibacterial effect of daptomycin has been observed only above this threshold concentration.…”

Section: Structure and Lps-membrane Interactionmentioning

confidence: 99%

Biophysical approaches for exploring lipopeptide-lipid interactions

et al. 2020

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a b s t r a c tIn recent years, lipopeptides (LPs) have attracted a lot of attention in the pharmaceutical industry due to their broad-spectrum of antimicrobial activity against a variety of pathogens and their unique mode of action. This class of compounds has enormous potential for application as an alternative to conventional antibiotics and for pest control. Understanding how LPs work from a structural and biophysical standpoint through investigating their interaction with cell membranes is crucial for the rational design of these biomolecules. Various analytical techniques have been developed for studying intramolecular interactions with high resolution. However, these tools have been barely exploited in lipopeptide-lipid interactions studies. These biophysical approaches would give precise insight on these interactions. Here, we reviewed these state-of-the-art analytical techniques. Knowledge at this level is indispensable for understanding LPs activity and particularly their potential specificity, which is relevant information for safe application. Additionally, the principle of each analytical technique is presented and the information acquired is discussed. The key challenges, such as the selection of the membrane model are also been briefly reviewed.Published by Elsevier B.V. 1.2.

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Evaluation of Lipopeptide (Daptomycin) Aggregation Using Fluorescence, Light Scattering, and Nuclear Magnetic Resonance Spectroscopy

Cited by 28 publications

References 42 publications

The action mechanism of daptomycin

The action mechanism of daptomycin

The interaction mechanism between lipopeptide (daptomycin) and polyamidoamine (PAMAM) dendrimers

Biophysical approaches for exploring lipopeptide-lipid interactions

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