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

The aggregation behavior and critical aggregation concentration (CAC) values of daptomycin in aqueous solutions were evaluated under the external factors of pH, temperature, daptomycin concentration, and calcium ions concentration by using the complementary characterization techniques, fluorescence,...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2014-03, Vol.103 (3), p.853-861
Main Authors: Qiu, Jiang, Kirsch, Lee E.
Format: Article
Language:English
Subjects:
analytical chemistry
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - metabolism
Calcium Signaling
daptomycin
Daptomycin - chemistry
Daptomycin - metabolism
Drug Stability
dynamic light scattering
Fluorescence Resonance Energy Transfer
fluorescence spectroscopy
Hot Temperature
Hydrogen-Ion Concentration
Ionophores - chemistry
Ionophores - metabolism
Kinetics
Kynurenic Acid - chemistry
Kynurenine - chemistry
Kynurenine - metabolism
lipopeptide antibiotic
Nephelometry and Turbidimetry
NMR spectroscopy
Nuclear Magnetic Resonance, Biomolecular
Osmolar Concentration
Particle Size
peptide aggregation
Protein Stability
Solubility
Spectrophotometry, Ultraviolet
spectroscopy
static light scattering
Tryptophan - chemistry
zwitterion
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Summary:The aggregation behavior and critical aggregation concentration (CAC) values of daptomycin in aqueous solutions were evaluated under the external factors of pH, temperature, daptomycin concentration, and calcium ions concentration by using the complementary characterization techniques, fluorescence, dynamic and static light scattering, and nuclear magnetic resonance (NMR) spectroscopy. On the basis of the intrinsic fluorescence resonance energy transfer of daptomycin, the CAC values were identified by an upward inflection of the fluorescence emission from Kyn-13 at 460nm. The pH-dependent CAC values were determined to be 0.14mM at pH 3.0, 0.12mM at pH 4.0, and 0.20mM at pH 2.5 and 5.0. The CAC values obtained by fluorescence spectroscopy were confirmed by dynamic light scattering and NMR spectroscopy.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.23859