Proton magnetic resonance spectra of thiocarboxamides

Dudek, Emily P.; Dudek, Gerald O.

doi:10.1021/jo01278a074

Cited by 46 publications

(21 citation statements)

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“…16–19 The thioamide NH is a stronger hydrogen bond donor than the oxoamide NH, while the sulfur is a slightly weaker hydrogen bond acceptor than the corresponding oxygen. 20–23 The thioamide sulfur is also more reactive as a nucleophile, reactivity commonly observed in cyclization during Edman degradation. 24,25 Despite these differences, the thioamide is generally stable at physiological pH and can be incorporated in an α-helix or a β-turn without grossly perturbing secondary structure.…”

Section: Introductionmentioning

confidence: 99%

Native Chemical Ligation of Thioamide-Containing Peptides: Development and Application to the Synthesis of Labeled α-Synuclein for Misfolding Studies

Batjargal

Wang²,

Goldberg³

et al. 2012

J. Am. Chem. Soc.

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Thioamide modifications of the peptide backbone are used to perturb secondary structure, to inhibit proteolysis, as photoswitches, and as spectroscopic labels. Thus far, their incorporation has been confined to single peptides synthesized on solid phase. We have generated thioamides in C-terminal thioesters or N-terminal Cys fragments and examined their compatibility with native chemical ligation conditions. Most sequence variants can be coupled in good yields with either TCEP or DTT as the reductant, though some byproducts are observed with prolonged TCEP incubations. Furthermore, we find that thioamides are compatible with thiazolidine protection of an N-terminal Cys, so that multiple ligations can be used to construct larger proteins. Since the acid-lability of the thioamide prohibits on-resin thioester synthesis using Boc chemistry, we devised a method for the synthesis of thioamide peptides with a masked C-terminal thioester that is revealed in situ. Finally, we have shown that thioamidous peptides can be coupled to expressed protein fragments to generate large proteins with backbone thioamide labels by synthesizing labeled versions of the amyloid protein α-synuclein for protein folding studies. In a proof-of-principle experiment, we demonstrated that quenching of fluorescence by thioamides can be used to track conformational changes during aggregation of labeled α-synuclein.

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Section: Introductionmentioning

confidence: 99%

Native Chemical Ligation of Thioamide-Containing Peptides: Development and Application to the Synthesis of Labeled α-Synuclein for Misfolding Studies

Batjargal

Wang²,

Goldberg³

et al. 2012

J. Am. Chem. Soc.

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“…1. Apart from sharing this feature the compounds are from various classes, such as nitroso (39) and azo-hydrazo (40)(41)(42) compounds, enamines (43)(44)(45), amides (12,46), thioamides (48)(49)(50)(51), carboxylic acids (38),ˇ-keto esters (10,11,13),ˇ-diketones (1-6, 14, 15),˛-acetyl-ˇ-diketones (7-9, 37, 47),ˇ-thioxoketones (52)(53)(54), hydroxyanthraquinones (16-18, 21, 22), hydroxynaphthoquinones (19,20,23,24), o-hydroxy aromatic ketones (25-30, 32-36, 37, 55) and esters (31). This range of compounds covers intramolecular hydrogen-bonded systems with oxygen, nitrogen and sulfur in the donors and acceptor functions.…”

Section: Introductionmentioning

confidence: 99%

Primary tritium and deuterium isotope effects on chemical shifts of compounds having an intramolecular hydrogen bond

Bolvig¹,

Hansen²,

Morimoto³

et al. 2000

Magn. Reson. Chem.

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The primary deuterium and tritium isotope effects, δ(XH) − δ(XD/T), were measured for 55 compounds having one or more intramolecular hydrogen bonds. The primary isotope effects were measured at various temperatures. For compounds displaying tautomerism the primary isotope effects are found to have contributions from both intrinsic and equilibrium isotope effects. The primary tritium isotope effect, PΔ(1H,3H), and the primary deuterium isotope effect, PΔ (1H,2H), are shown to be related by This finding is valid for both tautomeric compounds and compounds with localized hydrogen bonds. Large negative primary tritium and deuterium isotope effects were observed for compounds displaying tautomerism and having sulfur as donor or acceptor. These isotope effects show a strong temperature dependence, which is related to the change in equilibrium due to isotope substitution. For the compounds with localized hydrogen bonds, the primary deuterium and tritium isotope effects correlated with the two bond deuterium isotope effect on 13C chemical shifts. The primary deuterium and tritium isotope effects are therefore a measure of the hydrogen bond strength for compounds with localized hydrogen bonds. Copyright © 2000 John Wiley & Sons, Ltd.

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“…The electrostatic interactions associated with the hydrogen bond is formed between the two peptide units—one peptide as a hydrogen bond donor (peptide donor), and one peptide as hydrogen bond acceptor (peptide acceptor). Previous pKa and IR considerations61, 62 show a thiopeptide donor is favored over an oxopeptide donor. Moreover, an oxopeptide acceptor is favored over a thiopeptide acceptor.…”

Section: Resultsmentioning

confidence: 94%

Conformational analysis of thiopeptides: (ϕ,ψ) maps of thio‐substituted dipeptides

2001

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Noncoded amino acids such as isobutyric acid have been used extensively in the process of drug design and protein engineering. This article focuses on a noncoded amino acid where the oxygen in the peptide unit is replaced with a sp 2 sulfur. It was hypothesized that the conformational space as well as the conformational preferences of thiopeptides will be more restricted and altered by the bulkier atom with different electrostatic properties. In vacuo conformational minima as well as associated energies for the thio-substituted alanine dipeptides were calculated at the ab initio HF/6-31G * level. When the bulkier sulfur atom acts as a hydrogen bond acceptor in the C 5 conformation or in the C axial 7 and C equatorial 7 CONFORMATIONAL ANALYSIS OF THIOPEPTIDES S n−1 · · ·C β atoms, respectively. Thio substitution at the carboxyl terminal restricts the conformations near ψ = 60, −60, and 180, which correspond with increase overlaps between S n · · ·C β , S n · · ·H β and S n · · ·N n atoms, respectively. The effects of dithio substitutions of either the alanine or the glycine dipeptides are similar to the combined effects of the two single thio substitutions.

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Proton magnetic resonance spectra of thiocarboxamides

Cited by 46 publications

References 0 publications

Native Chemical Ligation of Thioamide-Containing Peptides: Development and Application to the Synthesis of Labeled α-Synuclein for Misfolding Studies

Native Chemical Ligation of Thioamide-Containing Peptides: Development and Application to the Synthesis of Labeled α-Synuclein for Misfolding Studies

Primary tritium and deuterium isotope effects on chemical shifts of compounds having an intramolecular hydrogen bond

Conformational analysis of thiopeptides: (ϕ,ψ) maps of thio‐substituted dipeptides

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