Structure and solvation of melittin in hexafluoroacetone/water

Gerig, J. T.

doi:10.1002/bip.20085

Cited by 15 publications

(20 citation statements)

References 31 publications

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“…[36] An inter-helix angle in this range has been observed for melittin in hexafluoroacetone/water solutions. [10,12] The values found for melittin in HFIP (73 ± 15 • ) [11] and in phosphatidylcholine vesicles (86 ± 34 • ) [37] appear to be exceptions in this regard. MD simulations indicate that the structure of melittin is highly dynamic in the HFIP solution, with two α-helical segments sampling a wide range of angular orientations.…”

Section: Peptide Structurecontrasting

confidence: 46%

“…TFE was present at 42% (v/v) since this concentration provides approximately the same molar concentration of fluorine as is present in 35% HFIP [11] or 50% hexafluoroacetone trihydrate. [12] NMR spectra were collected at a proton frequency of 500 MHz using a Varian INOVA instrument equipped with a 5-mm Nalorac proton/fluorine probe having a z-axis gradient capability. Sample temperatures were regulated by the instrument controller and were calibrated using a standard sample of methanol (Wilmad).…”

Section: Methodsmentioning

confidence: 99%

“…These shifts were generally within 0.1 ppm of the corresponding shifts observed in the solvents HFIP/water or hexafluoroacetone/water. [11,12] The tertiary structure of melittin in TFE/water was determined by conventional methods through analysis of H-H distance constraints indicated by intramolecular 1 H{ 1 H} NOEs. Further details of these structure determinations are provided in the Supporting Information.…”

Section: Peptide Structurementioning

confidence: 99%

“…[9,10] There are indications from NMR experiments that HFIP and hexafluoroacetone associate to some extent, for times of the order of nanoseconds, with all or parts of the melittin helix. [11,12] In the present work, we have used intermolecular solvent-solute nuclear Overhauser effect (NOE) experiments [13] to examine interactions of TFE with melittin.…”

Section: Introductionmentioning

confidence: 99%

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Interactions of 2,2,2‐trifluoroethanol with melittin

Neuman¹,

Gerig²

2009

Magnetic Reson in Chemistry

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Melittin dissolved in 42% trifluoroethanol-water at pH 2 has been shown to be alpha-helical between residues 6 and 12 and between residues 13 and 25, with the two helical regions separated by a bend at the Leu13 residue. The inter-helix angle was found to be 154 +/- 3 degrees at 0 degrees C and 135 +/- 3 degrees at 25 degrees C. The dominant conformation of the peptide is thus similar to those observed by previous workers for the peptide in a variety of media. At 25 degrees C, intermolecular nuclear Overhauser effects arising from nuclear spin dipole-dipole interactions between melittin hydrogens and fluorines of the solvent are essentially those expected for a system that is homogeneous as regards concentration and translational diffusion of the peptide and fluoroalcohol components. However, at 0 degrees C, peptide-trifluoroethanol cross-relaxation terms are negative, a result consistent with the conclusion that fluoroalcohol molecules associate with the peptide for times (approximately 1 ns) that are long compared to the time of a typical peptide-fluoroalcohol diffusive encounter (approximately 0.2 ns). Such interactions may be responsible for the reduction of the translational diffusion coefficient of trifluoroethanol produced by dissolved peptides.

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Section: Peptide Structurecontrasting

confidence: 46%

Section: Methodsmentioning

confidence: 99%

Section: Peptide Structurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Interactions of 2,2,2‐trifluoroethanol with melittin

Neuman¹,

Gerig²

2009

Magnetic Reson in Chemistry

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“…30,38,40,[48][49][50] Should such associations persist long enough, dipolar interactions between peptide hydrogens and solvent fluorines come to resemble intramolecular interactions, with the motions modulating HÀ ÀF interactions within the complex taking place on a slower time scale than the time characteristic of simple diffusive encounters. A negative NOE can be the result.…”

mentioning

confidence: 97%

Conformations of Betanova in aqueous trifluoroethanol

Chagolla

Gerig

2010

Biopolymers

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Conformations of the designed peptide Betanova in 42% trifluoroethanol/water (v/v) were explored. Circular dichroism (CD) observations provided no evidence for the presence of significant amounts of beta-structures in water, in TFE/water, or in ethanol/water. Nuclear magnetic resonance (NMR) diffusion experiments showed no significant difference in the hydrodynamic radius of the peptide in water and in 42% TFE/water. However, calculations indicated that the hydrodynamic radii of the triple-stranded beta-sheet, originally proposed for Betanova by Kortemme et al. (Science 1998, 281, 253-256), and a variety of partially folded forms of Betanova would be similar and likely could not be convincingly distinguished by diffusion experiments. Temperature coefficients (Deltadelta/DeltaT) of the peptide N--H chemical shifts are similar in water and 42% TFE/water, implying that most of these protons are highly solvent exposed in both solvents and likely do not participate in intramolecular hydrogen bonding interactions. Possible exceptions to this conclusion are the Lys9 and Lys15 residues, where a more positive coefficient may indicate that these residues are involved to some extent in local turn structures. Peptide proton-solvent fluorine intermolecular nuclear Overhauser effect (NOE)s at 25 degrees C were consistent with the presence of a mixture of conformations, which could include the triple-stranded beta-sheet structure as a minor component. At 0 degrees C, peptide-TFE NOEs indicated that TFE interacts strongly enough with many protons of Betanova that alcohol-peptide interactions persist for times of the order of nanoseconds, appreciably longer than the encounter time characteristic of mutual diffusion of TFE and the solute.

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Stability of a Trivalent Recombinant Protein Vaccine Formulation Against Botulinum Neurotoxin During Storage in Aqueous Solution

Vessely

Estey

Randolph

et al. 2009

Journal of Pharmaceutical Sciences

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The adsorption of recombinant botulinum neurotoxin (BoNT) protein-derived vaccine antigens to aluminum salt adjuvants has been previously studied for the development of a trivalent vaccine against the neurotoxins1. The current paper describes an investigation of the stability of recombinant BoNT antigens adsorbed to aluminum salt adjuvants during storage in aqueous solution. Both chemical and physical changes occurred during storage. Phosphate groups in the buffer exchanged with hydroxyl groups on the adjuvant surface. The resulting changes in solution pH and adjuvant surface chemistry promoted more favorable electrostatic interaction between the BoNT proteins and the surface, possibly increasing the affinity of the proteins for the surface during storage. Fluorescence and UV spectroscopy suggested changes to protein structure during storage, whereas differential scanning calorimetry showed changes to thermal processes related to protein conformation and/or surface adsorption. The consequence of the chemical and physical changes to the proteins was a decrease in the ability to desorb protein from the adjuvant surface during storage. Overall, the results of this study emphasize the utility of a thorough characterization of the interactions between protein antigens and aluminum salt adjuvants.

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Structure and solvation of melittin in hexafluoroacetone/water

Cited by 15 publications

References 31 publications

Interactions of 2,2,2‐trifluoroethanol with melittin

Interactions of 2,2,2‐trifluoroethanol with melittin

Conformations of Betanova in aqueous trifluoroethanol

Stability of a Trivalent Recombinant Protein Vaccine Formulation Against Botulinum Neurotoxin During Storage in Aqueous Solution

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