The solid state and solution structure of HAPyU.
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Crystallography, X-Ray↗
Biomedical subjects
C Mügge
Publications and source records attributed to C Mügge.
Structure determination and by-product profile of the NK(2) receptor antagonist nepadutant, a bicyclic glycopeptide.
We have synthesized and fully characterized the NK(2) receptor antagonist nepadutant and its by-products using nuclear magnetic resonance (NMR) and restrained molecular dynamics. The agent consists of an active bicyclic hexapeptide combined with a sugar residue. Analysis of the high-performance liquid chromatogram and the mass spectroscopy spectra yields traces of three by-products with the same molecular weight as the main product. The conformation of the molecules in the bicyclic hexapeptide segment, the active region, is well defined, whereas the sugar moiety is disordered. For the peptide region of nepadutant and all of its by-products, the NMR observables can be described by a single backbone conformation, more specifically a betaI, betaII-turn arrangement. The active dipeptide unit Trp-Phe occupies the i+1 and i+2 position of a betaI-turn. The by-product profile is characterized by different forms of sugars which are caused mainly by isomerization in the process of ring opening.
Chromatography, High Pressure Liquid↗
Actaeaepoxide 3-O-beta-D-xylopyranoside, a new cycloartane glycoside from the rhizomes of Actaea racemosa (Cimicifuga racemosa).
A new cycloartane glycoside (1) was obtained from a minor triterpene fraction of the rhizome extract of Actaea racemosa (synonym: Cimicifuga racemosa) along with a known compound, cimigenol 3-O-beta-D-xylopyranoside. The structure of 1 was elucidated as 20(S),22(R),23(R),24(S)-12beta-acetoxy-16beta:23,23alpha:24-diepoxy-3beta,22beta,25-trihydroxy-9,19-cyclolanost-7-ene 3-O-beta-D-xylopyranoside (actaeaepoxide 3-O-beta-D-xylopyranoside) on the basis of spectral and chemical evidence.
Chromatography, Gas↗
A bichalcone from the twigs of Rhus pyroides.
The twigs of Rhus pyroides yielded a novel bichalcone 2',4",2"'-trihydroxy-4',4"'-dimethoxy-4-O-5"'-bichalcone. It was identified on the basis of spectroscopic data including 1D and 2D NMR spectroscopy. The name rhuschalcone-1 is proposed.
Chalcone↗
Mimicry of beta II'-turns of proteins in cyclic pentapeptides with one and without D-amino acids.
The solution structure of eight cyclic pentapeptides has been determined by two-dimensional 1H-NMR spectroscopy combined with spectra simulations and restrained molecular dynamic simulations. Six of the cyclic pentapeptides were derived from the C-terminal cholecystokinin fragment CCK-4 enlarged with Asp1 resulting in the sequence (Asp-Trp-Met-Asp-Phe), one L-amino acid after the other was substituted by its D-analog. In addition, two peptides, including an all-L-amino-acid-containing cyclic pentapeptide, cyclo(Asp-Phe-Lys-Ala-Thr) and cyclo(Asp-Phe-Lys-Ala-D-Thr) were investigated. All D-amino-acid-containing peptides show beta II'-turn conformations with the D-amino acid in the i + 1 position, excepting the D-aspartic-acid-containing peptides. These two peptides are characterized by the lack of beta-turns at pH values less than 4, suggesting that D-aspartic acid in the full-protonized state avoids the formation of beta-turns in these compounds. At pH values greater than 5, a conformational change into the beta II'-turn conformation was also observed for these peptides. Conformations without beta-turns are expected for cyclic all-L pentapeptides, but both cyclo(Asp-Phe-Lys-Ala-Thr) and the D-Thr analog cyclo(Asp-Phe-Lys-Ala-D-Thr) exhibit beta II'-turn conformations around Thr-Asp and D-Thr-Asp. Thus cyclic all-L pentapeptides and those with one D-amino acid are able to form similar structures preferably with a beta II'-turn. The beta-turn formation in cyclic pentapeptides containing a D-aspartic acid is dependent on the ionization state. The relevance of the work to the design of beta'-turn mimetics is discussed.
Hydrogen Bonding↗
The determination of trifluoroacetic acid in rat milk samples by 19F-NMR spectroscopy and capillary gas chromatography.
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Animals↗
Application of on-line HPLC-1H NMR to environmental samples: analysis of groundwater near former ammunition plants.
Coupling of HPLC to NMR was applied for the first time to the analysis of environmental samples, i.e., water samples from an ammunition hazardous waste site. Using the continuous flow mode at very low flow rates (< or = 0.017 mL/min) and large volume injection (400 microL), the confirmation of many nitroaromatic compounds could be achieved down to the microgram-per-liter level after solid phase extraction of a groundwater sample from a former ammunition production site. At a flow rate of 0.006 mL/min, it is possible to detect less than 29 nmol (5 micrograms) of 1,3-dinitrobenzene injected on a 75 mm x 4 mm reversed phase C-18 column (particle size, 5 microns). The results obtained by HPLC-NMR are compared to those obtained by HPLC-PDA (photodiode array) of the same sample, demonstrating that many more compounds can be identified by the former compared to the latter method as a result of coelution of major and minor components in the HPLC chromatogram.
Chromatography, High Pressure Liquid↗
Comparison of proline and N-methylnorleucine induced conformational equilibria in cyclic pentapeptides.
The cyclic, imido acid containing pentapeptides cyclo(Asp-Trp-(NMe)Nle-Asp-Phe) (cpp[NMeNle(3)]) and cyclo(Asp-Trp-Pro-Asp-Phe) (cpp[Pro(3)]) have been investigated by 1H-NMR spectroscopy in DMSO and by restrained molecular dynamics methods. The spectra indicate the existence of at least four cis/trans isomers for cpp[NMeNle(3)] and two cis/trans isomers for cpp[Pro(3)]. In addition to the imido peptide bonds, cpp[NMeNle(3)] shows cis/trans isomerization of the Asp4-Phe5 and Phe5-Asp1 peptide bonds whereas only the Phe5-Asp1 peptide bond isomerizes in the Pro-containing peptide. In cpp[Pro(3)] all cis bonds are centred in betaVIb turns. Also, cpp[NMeNle(3)] prefers backbone angles around the cis bonds which are rather similar to the angles of a betaVIb turn. The higher number of cis/trans isomers and slight deviations in the backbone angles of comparable isomers of both peptides are caused by an enhanced flexibility of cpp[NMeNle(3)] due to the possibility of the phi-(NMe)Nle rotation.
Amino Acid Sequence↗
Temperature coefficients of amide proton NMR resonance frequencies in trifluoroethanol: a monitor of intramolecular hydrogen bonds in helical peptides.
2D 1H NMR spectroscopy of two alpha-helical peptides which differ in their amphipathicity has been used to investigate the relationships between amide-proton chemical shifts, amide-proton exchange rates, temperature, and trifluoroethanol (TFE) concentration. In 50% TFE, in which the peptides are maximally helical, the amide-proton chemical shift and temperature coefficient patterns are very similar to each other in each peptide. Temperature coefficients from -10 to -6 ppb/K, usually indicative of the lack of intramolecular hydrogen bonds, were observed even for hydrophobic amino acids in the center of the alpha-helices. However, slow hydrogen isotope exchange for residues from 4 to 16 in both 18-mer helices indicates intact intramolecular hydrogen bonds over most of the length of these peptides. Based on these anomalous observations, we suggest that the pattern of amide-proton shifts in alpha-helices in H20/TFE solvents is dominated by bifurcated intermolecular hydrogen-bond formation between the backbone carbonyl groups and TFE. The amide-proton chemical shift changes with increasing temperature may be interpreted by a disruption of intermolecular hydrogen bonds between carbonyl groups and the TFE in TFE/water rather than by the length of intramolecular hydrogen bonds in alpha-helices.
Hydrogen↗
Novel disulfide-constrained pentapeptides as models for beta-VIa turns in proteins.
The conformational behavior of cyclic peptides of the amino acid sequence Cys-Phe/Ala-Pro-Ala-Cys has been investigated through the combined use of molecular simulation methods and NMR experiments to find models for beta-VIa turns of proteins. Both oxidized (cyclic) peptides and reduced (linear) forms were investigated. At least 95% of the cyclic peptides show a cis conformation of the Xaa-Pro bond in solution in DMSO or water, whereas all other peptide bonds are trans. Furthermore, we observed a hydrogen bond between the NH group of residue Ala4 and the C = O group of residue Cys1. Both properties are indicative of beta-VIa turns. After reduction of the disulfide bridge, the all-trans form of the peptide bonds predominates.
Base Sequence↗
Cyclic cholecystokinin-analog pentapeptide cyclo (Asp-Trp-Met-Asp-Phe): an unexpected solution conformation.
The conformational analysis of the CCK-B binding peptide cyclo (Asp-Trp-Met-Asp-Phe) has been carried out in DMSO-d6 and in a mixture of H2O/DMSO-d6 by NMR spectroscopy and by restrained molecular dynamics methods. In the NMR spectra, only one set of resonance signals was found. The NOE analyses proved the existence of an all-trans conformation for this peptide. Distance constraints of 1H pairs derived from NOE data were used for restrained molecular dynamics simulations, resulting in one conformational family with a very regular orientation of the amino acids and similar dihedral angles for each residue. The dihedrals and the absence of an intramolecular hydrogen bond indicate that there is no common turn formation in the peptide backbone. A submicromolar binding constant for CCK-B receptors point to a similarity with the bioactive conformation.
Amino Acid Sequence↗
Study of the membrane permeability of a paramagnetic metal complex on single cells by NMR microscopy.
A new procedure has been developed for investigating the ability of paramagnetic metal complexes to penetrate the plasma membrane of eukaryotic cells without decomposition. Defolliculated Xenopus laevis oocytes formed the biological system to test N,N-ethylenebis-(1,5,5-trimethyltetramic-acid-3-acetiminato) copper (II). An increase of the signal intensities in spin-echo (SE) images of oocytes treated with the tested substance indicated that the complex was able to penetrate biological membranes due to the arrangement of hydrophobic and hydrophilic groups within the ligand. In contrast, the treatment with the commonly used contrast agent gadolinium-DTPA/dimeglumine did not enhance the signal intensity in NMR images of oocytes after time periods of exposure comparable to those used for the copper complex. After microinjection into Xenopus oocytes the copper complex was released into the extracellular medium without degradation, as shown by HPLC measurements.
Animals↗
[Heat-induced decomposition of disaccharide Amadori compounds in quasi-water-free reaction conditions].
The thermally induced decomposition of disaccharide Amadori compounds has been compared to those of monosaccharide ones under almost water-free conditions. The structure of the synthesized maltulosyl compound has been proved to be 4C1-alpha-D-glucopyranosyl- (1----4)-2C5-beta-D-fructopyranosylglycine by 1H- and 13C-NMR spectroscopy. The decomposition of Amadori compounds has been used to study the kinetics of the browning reaction. Compared to fructosylglycine and maltotriulosylglycine, the browning of the disaccharide is faster. Curie point pyrolysis at 300 degrees C and investigation of the pyrolysate by gas chromatography/mass spectrometry have shown that the disaccharide component influences the thermal process. Furanes and furanones have been detected as predominant degradation products, the main one being 2(5H)-furanone. For the first time, we suggest a reaction pathway for the formation of these products via the Maillard reaction which includes 1,6-anhydroglucose.
Disaccharides↗