Dehydroalanine Residues in Thiostrepton

Bodanszky, Miklos; Scozzie, James A.; Muramatsu, Ichiro

doi:10.7164/antibiotics.23.9

Cited by 25 publications

(9 citation statements)

References 6 publications

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“…This observation is similar to that found for thiostrepton7, 8), and suggests that the thiopeptin B molecule also contains one residue of 2-aminocrotonic acid (dehydrobutyrine) and two residues of 2-aminoacrylic acid (dehydroalanine). This was substantiated further by formation of the 2,4-dinitrophenylhydrazones of 2-ketobutyric and pyruvic acids after acid-hydrolysis of thiopeptin B.…”

supporting

confidence: 85%

Amino acids and derivatives of thiazole-4-carboxylic acid as constituents of thiopeptin B.

Muramatsu¹,

Motoki²,

Aoyama³

et al. 1977

J. Antibiot.

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supporting

confidence: 85%

Amino acids and derivatives of thiazole-4-carboxylic acid as constituents of thiopeptin B.

Muramatsu¹,

Motoki²,

Aoyama³

et al. 1977

J. Antibiot.

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“…[8] Recently, thiostrepton was reported to exhibit activity against breast cancer cells. [10] We found that homogeneous catalysis with [Rh(cod)(diop)]BF 4 (cod = 1,5-cyclooctadiene, diop = 2,2-dimethyl-1,3-dioxolane-4,5-diylbis(methylene)bis(diphenylphosphine)) for one hour at room temperature in a 4:1 mixture of CHCl 3 /MeOH gave a 90 % yield of hydrogenated product 4 (Scheme 1). [10] We found that homogeneous catalysis with [Rh(cod)(diop)]BF 4 (cod = 1,5-cyclooctadiene, diop = 2,2-dimethyl-1,3-dioxolane-4,5-diylbis(methylene)bis(diphenylphosphine)) for one hour at room temperature in a 4:1 mixture of CHCl 3 /MeOH gave a 90 % yield of hydrogenated product 4 (Scheme 1).…”

mentioning

confidence: 99%

“…[9] The hydrogenation reaction of thiostrepton with a heterogeneous Pd/C catalyst was reported, but required harsh conditions and long reaction times. [10] We found that homogeneous catalysis with [Rh(cod)(diop)]BF 4 (cod = 1,5-cyclooctadiene, diop = 2,2-dimethyl-1,3-dioxolane-4,5-diylbis(methylene)bis(diphenylphosphine)) for one hour at room temperature in a 4:1 mixture of CHCl 3 /MeOH gave a 90 % yield of hydrogenated product 4 (Scheme 1). Thiostrepton possesses several unsaturated groups in the structure, including three dehydroalanines (deAla) and a dehydrobutyrine (But).…”

mentioning

confidence: 99%

Peptide Hydrogenation and Labeling with Parahydrogen

Gruppi

Zhang

et al. 2012

Angew Chem Int Ed

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The assignment of specific fragments of peptides or proteins in NMR spectra can be challenging for complex structures with overlap of signals possessing similar chemical shifts. One attractive choice to address this issue is the use of isotopically labeled molecules. The labeling process may be difficult, however, for naturally occurring biomolecules. Recently, the use of hyperpolarized molecules has attracted much attention. Hyperpolarized 129 Xe gas has been used to examine protein interactions and binding dynamics. [1] Dynamic nuclear polarization (DNP) methods, including chemically and photochemically induced polarization (CIDNP) can be used to obtain information, including structural features and folding dynamics of proteins. [2] Herein, we demonstrate hyperpolarization of the naturally occurring peptide antibiotic, thiostrepton, selectively at terminal dehydroalanine residues using parahydrogen-induced polarization (PHIP). [3] This approach revealed NMR spectral features for the hydrogenated residues among heavily overlapped peaks, demonstrating sitespecific spin polarization labeling of a biomolecule. Surprisingly, polarization transfer to a remote alanine residue was also observed. The diastereoselectivity of the hydrogenation reaction was determined using PHIP in conjunction with other data. These results show that parahydrogen can be used to enhance signals and elucidate the hydrogenation process of dehydropeptide units in complex biomolecules.PHIP is an efficient and economical strategy to gain a substantial signal boost. [3] In this method, polarization enhancement can be achieved either by direct hydrogenation, or by reversible polarization exchange in intermediate processes. In the signal amplification by reversible exchange (SABRE) approach, [4] the polarization is exchanged from parahydrogen (p-H 2 ) to the target molecule via an organometallic intermediate complex. SABRE achieves polarization transfer without permanently altering the chemical structure of the substrate, but not all molecules can be polarized, and only particular examples of relatively small molecules have been polarized effectively to date. [4a,c] The other method, involving hydrogenation with p-H 2 , is relatively simple to implement and, in principle, can be performed on any sample possessing an asymmetric multiple bond. In this case also, only relatively simple molecules have been examined by this method to date. [5] As an example of applying PHIP methods to molecules typical of those found in biology, we describe herein the monitoring of a homogeneous hydrogenation reaction with Rh I complexes, taking advantage of the "only parahydrogen spectroscopy" (OPSY) technique [6] for the analysis of reaction stereoselectivity and conformational dynamics of peptide units.Although in prior work the hydrogenation of a dehydroamino acid derivative was demonstrated, [7] scaling up the procedure to larger molecules is nontrivial. Herein, we sought to examine a peptide by PHIP. Thiostrepton (Scheme 1) is a naturally occurring antibiotic...

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“…The hydrogenation reaction of thiostrepton with a heterogeneous Pd/C catalyst was reported, but required harsh conditions and long reaction times 10. We found that homogeneous catalysis with [Rh(cod)(diop)]BF 4 (cod=1,5‐cyclooctadiene, diop=2,2‐dimethyl‐1,3‐dioxolane‐4,5‐diylbis(methylene)bis(diphenylphosphine)) for one hour at room temperature in a 4:1 mixture of CHCl 3 /MeOH gave a 90 % yield of hydrogenated product 4 (Scheme ).…”

Section: Methodsmentioning

confidence: 99%

Peptide Hydrogenation and Labeling with Parahydrogen

Gruppi¹,

Xu²,

Zhang³

et al. 2012

Angewandte Chemie

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Die ortspezifische Spinpolarisationsmarkierung eines Peptids gelang durch homogene Hydrierung mit Parawasserstoff. Überraschenderweise trat ein Polarisationstransfer auf einen entfernt liegende Alaninrest auf. Die Diastereoselektivität der Hydrierung wurde bestimmt, und die Ergebnisse zeigen, dass sich Parawasserstoff zur Signalverstärkung und Aufklärung der Hydrierungsmechanismen von Dehydropeptid‐Einheiten in komplexen Molekülen eignet.

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Dehydroalanine Residues in Thiostrepton

Cited by 25 publications

References 6 publications

Amino acids and derivatives of thiazole-4-carboxylic acid as constituents of thiopeptin B.

Amino acids and derivatives of thiazole-4-carboxylic acid as constituents of thiopeptin B.

Peptide Hydrogenation and Labeling with Parahydrogen

Peptide Hydrogenation and Labeling with Parahydrogen

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