Experimental and quantum-chemical studies of the dipole moments of quinoline and indole

Weiler‐Feilchenfeld, Hannah; Pullman, Alberte; Berthod, Hélène; Giessner‐Prettre, Claude

doi:10.1016/0022-2860(70)90013-x

Cited by 32 publications

(94 citation statements)

References 15 publications

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“…52 The 1 L a excited state in 5FW and 6FW has a larger dipole moment than that of un-substituted Trp. 53, 54 Consequently, the excited state in fluoro-Trp derivatives is preferentially stabilized by solvation in polar environments compared to un-substituted Trp. 55 Thus, incorporation of 5FW or 6FW at a solvent-exposed site is expected to lead to more strongly red-shifted fluorescence emission than for a buried site.…”

Section: Resultsmentioning

confidence: 99%

Fluorotryptophan Incorporation Modulates the Structure and Stability of Transthyretin in a Site-Specific Manner

2017

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Abnormal deposition of aggregated wild-type (WT) human transthyretin (TTR) and its pathogenic variants is responsible for cardiomyopathy and neuropathy related to TTR amyloidosis. The tryptophan (Trp) fluorescence measurements typically used to study structural changes of TTR do not yield site-specific information on the two Trp residues per TTR protomer. To obtain such information, tryptophan labeled with fluorine at the 5 and 6 positions (5FW and 6FW) was incorporated into TTR. Fluorescence of 5FW and 6FW-labeled WT-TTR (WT-5FW and WT-6FW) and a single-Trp mutant W41Y showed that the photophysics of incorporated fluoro-Trp is consistent with site-specific solvation of the indole ring of W41 and W79. 19F-NMR showed that solvent accessibility depends on both the location of the Trp and the position of the fluorine substituent in the indole ring. Unexpectedly, differences were observed in the rates of aggregation, with WT-6FW aggregating more rapidly than WT-5FW or WT TTR. Real-time 19F-NMR urea unfolding experiments revealed that WT-5FW is kinetically more stable than WT-6FW, consistent with the aggregation assay. In addition, structural perturbations of residues distant from either Trp site are more extensive in WT-6FW. Notably, residues in the dimer interfaces are perturbed by 6FW at residue 79; pathogenic mutations in these regions are associated with reduced tetramer stability and amyloidogenesis. The differences in behavior that arise from the replacement of a fluorine at the 5-position of a tryptophan with one at the adjacent 6-position emphasizes the delicate balance of stability in the TTR tetramer.

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Section: Resultsmentioning

confidence: 99%

Fluorotryptophan Incorporation Modulates the Structure and Stability of Transthyretin in a Site-Specific Manner

2017

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“…Phe like Trp is an aromatic amino acid, but is less polar and lacks hydrogen-bonding ability, whereas Trp is amphipathic and able to be a hydrogen-bond donor by means of the indole NH group. Trp furthermore has a dipole moment of ≈ 2 Debye along the C5→N1 axis (13). The observed conformational shift thus may be due to these differences between the Trp and Phe side chain characteristics, with the hydrogen bond formation likely to be dominant (17).…”

Section: Discussionmentioning

confidence: 99%

“…Trp is a large aromatic, amphiphilic amino acid with a dipole moment of ≈ 2 Debye along the C5→N1 axis (13). Substitutions of Trp by the more hydrophobic Phe have revealed important information about gA channels.…”

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confidence: 99%

The Membrane Interface Dictates Different Anchor Roles for “Inner Pair” and “Outer Pair” Tryptophan Indole Rings in Gramicidin A Channels

Lum

Kim

et al. 2011

Biochemistry

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We investigated the effects of substituting two of the four tryptophans (the “inner pair” Trp9,11 or the “outer pair” Trp13,15) in gramicidin A (gA) channels. The conformational preferences of the double-substituted gA analogues were assessed using circular dichroism spectroscopy and size-exclusion chromatography, which show that the inner tryptophans 9 and 11 are critical for the gA’s conformational preference in lipid bilayer membranes. [Phe13,15]gA largely retains the single-stranded helical channel structure, whereas of [Phe9,11]gA exists primarily as double-stranded conformers. Within this context, the 2H-NMR spectra from labeled tryptophans were used to examine the changes in average indole ring orientations, induced by the Phe substitutions and by the shift in conformational preference. Using a method for deuterium labeling of already synthesized gAs, we introduced deuterium selectively onto positions C2 and C5 of the remaining tryptophan indole rings in the substituted gA analogues for solid-state 2H-NMR spectroscopy. The (least possible) changes in orientation and overall motion of each indole ring were estimated from the experimental spectra. Regardless of the mixture of backbone folds, the indole ring orientations observed in the analogues are similar to those found previously for gA channels. Both Phe-substituted analogues form single-stranded channels, as judged from the formation of heterodimeric channels with the native gA. [Phe13,15]gA channels have Na+ currents that are ~50% and lifetimes ~80% those of native gA channels. The double-stranded conformer(s) of [Phe9,11]gA do not form detectable channels. The minor single-stranded population of [Phe9,11]gA forms channels with Na+ currents that are ~25% and single-channel lifetimes that are ~300% those of native gA channels. Our results suggest that Trp9 and Trp11, when “reaching” for the interface, tend to drive both monomer folding (to “open” a channel) and dimer dissociation (to “close” a channel). Furthermore, the dipoles of Trp9 and Trp11 are relatively more important for the single-channel conductance than are the dipoles of Trp13 and Trp15.

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“…However, it is important to recognize that another signi®cant difference between Trp and either Tyr or Phe is the potential effect of their ring dipoles on face-to-face aromatic stacking interaction. Indole has a strong ®xed dipole of about 2.4 Debye oriented along the axis from positive at N1 to negative at C4 (Weiler-Feilchenfeld et al, 1970). A striking feature of the simulated Y88W structure is that these dipoles are arranged nearly antiparallel (Figure 3).…”

Section: Discussionmentioning

confidence: 87%

An aromatic stacking interaction between subunits helps mediate DNA sequence specificity: operator site discrimination by phage λ cI repressor

Huang

Rusinova

Ross

et al. 1997

Journal of Molecular Biology

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Experimental and quantum-chemical studies of the dipole moments of quinoline and indole

Cited by 32 publications

References 15 publications

Fluorotryptophan Incorporation Modulates the Structure and Stability of Transthyretin in a Site-Specific Manner

Fluorotryptophan Incorporation Modulates the Structure and Stability of Transthyretin in a Site-Specific Manner

The Membrane Interface Dictates Different Anchor Roles for “Inner Pair” and “Outer Pair” Tryptophan Indole Rings in Gramicidin A Channels

An aromatic stacking interaction between subunits helps mediate DNA sequence specificity: operator site discrimination by phage λ cI repressor

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