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Harms, Greg S.; Pauls, Steve W.; Hedstrom, John F.; Johnson, Carey K.

doi:10.1023/a:1022573825058

Cited by 27 publications

(32 citation statements)

References 24 publications

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“…Fluorescence decays were measured for samples in aqueous, urea, GdmCl, and proline from 0 to 5.5 M at 280 K, 290 K, and 300, 310, 320 K. Fluorescence decays for parallel and perpendicular polarizations were globally fit to a 3-exponential intensity decay coupled to a double-exponential anisotropy decay. Rotational correlation times for the NATA were obtained by globally fitting the fluorescence decays with polarizations parallel and perpendicular to the excitation polarization as described elsewhere . The initial anisotropy r (0) at t = 0 is kept fixed at 0.25 in the fitting procedure as described elsewhere .…”

Section: Methodsmentioning

confidence: 99%

Probing Selection Mechanism of the Most Favorable Conformation of a Dipeptide in Chaotropic and Kosmotropic Solution

2016

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Chaotropes like urea and guanidinium chloride (GdmCl) tend to destabilize, and kosmotropes like proline tend to stabilize folded structures of peptides and proteins. Here, we combine fluorescence anisotropy decay measurements and molecular dynamics simulations to gain a microscopic understanding of the molecular mechanism for shifting conformational preferences in aqueous, GdmCl, urea, and proline solutions of a simple model dipeptide, N-acetyl-tryptophan-amide (NATA). Measured anisotropy decay of NATA as a function of temperature, pH, and cosolvent concentrations showed reorientations moderately slower in GdmCl and urea and substantially slower in proline compared to those of aqueous environment. A small change in pH significantly slows orientation time in water and GdmCl and less markedly in urea. Computationally, we use molecular dynamics with dihedral restraints to separately analyze the motions and interactions of the representative NATA conformers in the four different solvent environments. This novel analysis provides a dissection of the observed overall diffusion rates into contributions from individual dipeptide conformations. The variation of rotational diffusion rates with conformation are quite large. Population-weighted averaging or using properties of the major cluster reproduces the dynamical features of the full unrestrained dynamics. Additionally, we correlate the observable diffusion rates with microscopic features of conformer size, shape, and solvation. This analysis uncovered underlying differences in detailed atomistic behavior of the three cosolvents-urea, GdmCl, and proline. For both urea and the pure water system we find good agreement with hydrodynamic theory, with diffusion rates primarily correlated with conformer size and shape. In contrast, for GdmCl and proline solutions, the variation in conformer diffusion rates was mostly determined by specific interactions with the cosolvents. We also find preferences for different molecular shapes by the three cosolvents, with increased preferential solvation of smaller and more spherical conformers by urea and larger and more elongated conformers by GdmCl and proline. Additionally, our results provide a basis for a simple approximate model of the effects of pH lowering on dipeptide conformational equilibria. The translational diffusion rates of NATA are less sensitive to conformations, but variation with solvation strength is similar to rotational diffusion. Our results, combining experiment and simulation, show that we can identify the individual peptide conformers with definite microscopic properties of shape, size, and solvation, that are responsible for producing physical observables, such as translational and orientational diffusion in the complex solvent environments of denaturants and osmolytes.

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Section: Methodsmentioning

confidence: 99%

Probing Selection Mechanism of the Most Favorable Conformation of a Dipeptide in Chaotropic and Kosmotropic Solution

2016

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“…Moreover, an increase in the Tyr decay time (s) is associated with the increased size of the biomolecule. 63,64 In this context, Amaro et al 63 illustrated that the lifetime increases substantially with an increase in the aggregation state of a protein. This occurs due to ionic and hydrogen bonding interactions which are common phenomena responsible for protein aggregation.…”

Section: Time Resolved Uorescencementioning

confidence: 99%

The stability of insulin in the presence of short alkyl chain imidazolium-based ionic liquids

Kumar

Venkatesu

2014

RSC Adv.

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Fibril or aggregation formation in insulin (In) has been a subject of severe biomedical and biotechnological complications. The search for a novel solvent/co-solvent that can provide long term stabilization for In monomeric form has not been completed yet. In this quest, for the first time we have successfully explored the stability of the monomeric form of In in the presence of ammonium-based ionic liquids (ILs) [A. Kumar and P. Venkatesu, RSC Adv., 2013, 3, 362-367]. Further, in continuation, in this study, we have established the stability of In in the presence of imidazolium-based ILs with different anions. These anions represent the Hofmeister series of anions of ILs. In this regard, we have carried out UV-vis, fluorescence, circular dichroism spectral analysis and dynamic light scattering (DLS) measurements of In in various concentrations of these ILs. Our experimental findings reveal that Br À and Cl À ILs stabilized the native state while the rest of the ILs with anions such as SCN À , HSO 4 À , CH 3 COO À and I À were denaturants for the In. Further, the results show that IL-In interactions are difficult to classify on the basis of the Hofmeister series, as bromide containing ILs show more stabilizing properties on the In structure. The disulfide bonds were almost intact in the presence of Br À IL as compared to Cl À and the rest of the Hofmeister anions. On the other hand, a strongly hydrated kosmotropic anion like HSO 4 À interacts with the structure of In, leading it towards complete denaturation of the In structure.Additionally, all ILs failed to protect the native state of In with increasing temperature.

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“…Previous measurements in our laboratory showed that tyrosine rotational diffusion in water and in 50% propylene glycol/water is characterized by a single rotational correlation time. 7,11 Thus, the double-exponential behavior uncovered here is not an intrinsic feature of tyrosine rotational diffusion. This suggests that the presence of two rotational components is the result of two distinct environments experienced by the tyrosine molecule, one with fast reorientation times characteristic of tyrosine in a fluid environment, and the other characterized by much longer rotational correlation times suggesting strong interaction with PVP.…”

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confidence: 68%

“…11 A regulated water bath (Neslab RTE-100) was used to control sample temperature by flowing ethylene glycol through the sample cell holder. The desired temperature was set prior to the experiment using a thermister (Omega HH501AK) placed in the cuvette.…”

Section: Fluorescence Measurementsmentioning

confidence: 99%

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Tyrosine and peptide reorientational mobility in polymer solutions: Time‐dependent fluorescence anisotropy measurements

2003

Self Cite

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The ability of peptides to form biologically active conformations that bind to receptors is governed by their dynamics and their propensity to form stable structures. Such factors are consequently important in the design of peptide drugs. Moreover, the stability of such peptides depends on interactions of the peptide with the surrounding matrix. In this article, we study the effect of the polymer poly(vinyl pyrrolidone) (PVP) on the mobility and orientational dynamics of tyrosine and a model peptide, Val-Tyr-Pro-Asn-Gly-Ala (VYPNGA) in glycerol-water solutions. Orientational dynamics are studied experimentally by time-resolved fluorescence anisotropy decays of tyrosine. The presence of PVP leads to the possibility of a distribution of environments for the peptide. The orientational dynamics of tyrosine show that the probe molecule experiences two very different environments. In one, tyrosine rotational motion is weakly coupled to PVP, while in the other, tyrosine interacts strongly with PVP leading to much slower rotational times. The dynamics of VYPNGA are more complex. Fast intramolecular, localized reorientations of the tyrosine are detected. The temperature dependence of the reorientational dynamics of the tyrosine side chain reveal that these motions are shielded from solvent friction. In contrast, global motions of the peptide are severely restricted by PVP, suggesting the ability of the polymer to restrict peptide mobility.

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Untitled

Cited by 27 publications

References 24 publications

Probing Selection Mechanism of the Most Favorable Conformation of a Dipeptide in Chaotropic and Kosmotropic Solution

Probing Selection Mechanism of the Most Favorable Conformation of a Dipeptide in Chaotropic and Kosmotropic Solution

The stability of insulin in the presence of short alkyl chain imidazolium-based ionic liquids

Tyrosine and peptide reorientational mobility in polymer solutions: Time‐dependent fluorescence anisotropy measurements

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