The Experts below are selected from a list of 9 Experts worldwide ranked by ideXlab platform
David C. Spellmeyer - One of the best experts on this subject based on the ideXlab platform.
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Synthesis, molecular modelling, and NMR structure determination of four cyclic peptide antagonists of endothelin
Bioorganic & medicinal chemistry, 1994Co-Authors: Erin K. Bradley, Reyna J. Simon, David C. SpellmeyerAbstract:Abstract A combined distance geometry and molecular mechanics/dynamics (MM/MD) protocol was unable to predict the active conformation of the cyclic pentapeptide inhibitor of endothelin-1 receptor, BQ-123, and two analogues. However, the MM/MD method alone is sufficient to predict the solution conformation of a third analogue. In that one case, the combination of proline at residue 3 and an N α -methyl substitution at residue 5 provides enough internal constraints to eliminate conformational flexibility seen in the other three analogues. For this constrained analogue, the 50 lowest energy conformations (out of a set of 500 DGEOM-generated, MM/MD minimized conformations) differ by no more than 3.9 kcal/mol. Thirty three of these 50 conformations have backbone atom RMSDs of less than 0.33 A, relative to the lowest energy conformation. The accuracy of this MM/MD model is verified by determining the solution structure of each of the four analogues with 2D NMR techniques. Each of the cyclic pentapeptides has a well defined solution conformation where a proline residue is clearly in a γ-turn, leaving the remaining residues in a loose β-turn. All four experimental NMR conformations agree closely with the MM/MD model. MM/MD molecular mechanics/molecular dynamics, DG distance geometry, RMS root mean square, RMSD root mean square deviation. NMR nuclear magnetic resonance, 2D NMR 2-dimensional NMR, ROESY 2-dimensional rotating frame nuclear Overhauser effect Spectroscopy, COSY 2-dimensional J-correlated Spectroscopy, PECOSY 2-dimensional Exclusive Correlation Spectroscopy, TOCSY 2-dimensional total Correlation Spectroscopy, 3 J Nα , NH-C α H vicinal proton coupling constant, 3 J αβ C α H-C β H vicinal proton coupling constant. FMOC 9-(fluorenylmethoxy)carbonyl, PyBOP benzotriazole-1-yl-oxy-tris-(pyrrolidino)phosphonium hexafluorophosphate, PyBrOP, bromo-tris-(pyrrolidino)phosphonium hexafluorophosphate, HOBt hydroxybenzotriazole, DMSO dimethyl sulfoxide, DCM dichloromethane, DMF dimethyl formamide, DIEA diisopropylethanolamine, TFA trifluoroacetic acid, EtOH ethanol, HOAc acetic acid, TMS tetramethylsilane, DMAP dimethylaminopyridine, DIC diisopropylcarbodiimide. RP-HPLC reverse phase high pressure liquid chromotography, AAA amino acid analysis, FAB-MS fast atom bombardment mass spectral analysis. We use the designations ETR A and ETR B , rather than the convention ET A and ET B to ensure clarity that we are discussing the two receptor subtypes of the Endothelin family.
Jürgen M. Schmidt - One of the best experts on this subject based on the ideXlab platform.
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Conformational Equilibria in Polypeptides. II. Dihedral-Angle Distribution in Antamanide Based on Three-Bond Coupling Information
Journal of Magnetic Resonance, 1997Co-Authors: Jürgen M. SchmidtAbstract:Abstract The use of3Jcoupling information in deriving dihedral-angle restraints for polypeptide-structure determination in the presence of conformational equilibria is illustrated withantamanide,cyclo(–Val1–Pro2– Pro3– Ala4– Phe5– Phe6– Pro7– Pro8– Phe9– Phe10–). The experimental basis comprises accurate three-bond coupling constants as obtained from both homonuclear [C. Griesinger, O. W. Sorensen, and R. R. Ernst,J. Magn. Reson.75,474 (1987)] and heteronuclear [J. M. Schmidt,J. Magn. Reson.124,298 (1997)] Exclusive Correlation Spectroscopy (E.COSY). For the backbone and side-chain dihedral angles in the nonproline residues, φ and χ1, respectively, probability-distribution functions are derived and evaluated on the basis of χ2statistics and significance estimates. Various motional models are considered in the quantitative compilation of molecular-geometry parameters from spin-system parameters. From the3Jcoupling analysis, antamanide is found to possess a very flexible structure which is consistent with the results previously obtained in homonuclear NOE and13C–T1relaxation studies. To fully agree with experiment, rotamer equilibria must be assumed for almost all of the torsions investigated in the peptide.
Erin K. Bradley - One of the best experts on this subject based on the ideXlab platform.
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Synthesis, molecular modelling, and NMR structure determination of four cyclic peptide antagonists of endothelin
Bioorganic & medicinal chemistry, 1994Co-Authors: Erin K. Bradley, Reyna J. Simon, David C. SpellmeyerAbstract:Abstract A combined distance geometry and molecular mechanics/dynamics (MM/MD) protocol was unable to predict the active conformation of the cyclic pentapeptide inhibitor of endothelin-1 receptor, BQ-123, and two analogues. However, the MM/MD method alone is sufficient to predict the solution conformation of a third analogue. In that one case, the combination of proline at residue 3 and an N α -methyl substitution at residue 5 provides enough internal constraints to eliminate conformational flexibility seen in the other three analogues. For this constrained analogue, the 50 lowest energy conformations (out of a set of 500 DGEOM-generated, MM/MD minimized conformations) differ by no more than 3.9 kcal/mol. Thirty three of these 50 conformations have backbone atom RMSDs of less than 0.33 A, relative to the lowest energy conformation. The accuracy of this MM/MD model is verified by determining the solution structure of each of the four analogues with 2D NMR techniques. Each of the cyclic pentapeptides has a well defined solution conformation where a proline residue is clearly in a γ-turn, leaving the remaining residues in a loose β-turn. All four experimental NMR conformations agree closely with the MM/MD model. MM/MD molecular mechanics/molecular dynamics, DG distance geometry, RMS root mean square, RMSD root mean square deviation. NMR nuclear magnetic resonance, 2D NMR 2-dimensional NMR, ROESY 2-dimensional rotating frame nuclear Overhauser effect Spectroscopy, COSY 2-dimensional J-correlated Spectroscopy, PECOSY 2-dimensional Exclusive Correlation Spectroscopy, TOCSY 2-dimensional total Correlation Spectroscopy, 3 J Nα , NH-C α H vicinal proton coupling constant, 3 J αβ C α H-C β H vicinal proton coupling constant. FMOC 9-(fluorenylmethoxy)carbonyl, PyBOP benzotriazole-1-yl-oxy-tris-(pyrrolidino)phosphonium hexafluorophosphate, PyBrOP, bromo-tris-(pyrrolidino)phosphonium hexafluorophosphate, HOBt hydroxybenzotriazole, DMSO dimethyl sulfoxide, DCM dichloromethane, DMF dimethyl formamide, DIEA diisopropylethanolamine, TFA trifluoroacetic acid, EtOH ethanol, HOAc acetic acid, TMS tetramethylsilane, DMAP dimethylaminopyridine, DIC diisopropylcarbodiimide. RP-HPLC reverse phase high pressure liquid chromotography, AAA amino acid analysis, FAB-MS fast atom bombardment mass spectral analysis. We use the designations ETR A and ETR B , rather than the convention ET A and ET B to ensure clarity that we are discussing the two receptor subtypes of the Endothelin family.
Reyna J. Simon - One of the best experts on this subject based on the ideXlab platform.
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Synthesis, molecular modelling, and NMR structure determination of four cyclic peptide antagonists of endothelin
Bioorganic & medicinal chemistry, 1994Co-Authors: Erin K. Bradley, Reyna J. Simon, David C. SpellmeyerAbstract:Abstract A combined distance geometry and molecular mechanics/dynamics (MM/MD) protocol was unable to predict the active conformation of the cyclic pentapeptide inhibitor of endothelin-1 receptor, BQ-123, and two analogues. However, the MM/MD method alone is sufficient to predict the solution conformation of a third analogue. In that one case, the combination of proline at residue 3 and an N α -methyl substitution at residue 5 provides enough internal constraints to eliminate conformational flexibility seen in the other three analogues. For this constrained analogue, the 50 lowest energy conformations (out of a set of 500 DGEOM-generated, MM/MD minimized conformations) differ by no more than 3.9 kcal/mol. Thirty three of these 50 conformations have backbone atom RMSDs of less than 0.33 A, relative to the lowest energy conformation. The accuracy of this MM/MD model is verified by determining the solution structure of each of the four analogues with 2D NMR techniques. Each of the cyclic pentapeptides has a well defined solution conformation where a proline residue is clearly in a γ-turn, leaving the remaining residues in a loose β-turn. All four experimental NMR conformations agree closely with the MM/MD model. MM/MD molecular mechanics/molecular dynamics, DG distance geometry, RMS root mean square, RMSD root mean square deviation. NMR nuclear magnetic resonance, 2D NMR 2-dimensional NMR, ROESY 2-dimensional rotating frame nuclear Overhauser effect Spectroscopy, COSY 2-dimensional J-correlated Spectroscopy, PECOSY 2-dimensional Exclusive Correlation Spectroscopy, TOCSY 2-dimensional total Correlation Spectroscopy, 3 J Nα , NH-C α H vicinal proton coupling constant, 3 J αβ C α H-C β H vicinal proton coupling constant. FMOC 9-(fluorenylmethoxy)carbonyl, PyBOP benzotriazole-1-yl-oxy-tris-(pyrrolidino)phosphonium hexafluorophosphate, PyBrOP, bromo-tris-(pyrrolidino)phosphonium hexafluorophosphate, HOBt hydroxybenzotriazole, DMSO dimethyl sulfoxide, DCM dichloromethane, DMF dimethyl formamide, DIEA diisopropylethanolamine, TFA trifluoroacetic acid, EtOH ethanol, HOAc acetic acid, TMS tetramethylsilane, DMAP dimethylaminopyridine, DIC diisopropylcarbodiimide. RP-HPLC reverse phase high pressure liquid chromotography, AAA amino acid analysis, FAB-MS fast atom bombardment mass spectral analysis. We use the designations ETR A and ETR B , rather than the convention ET A and ET B to ensure clarity that we are discussing the two receptor subtypes of the Endothelin family.
Andrew L. Pinchuck - One of the best experts on this subject based on the ideXlab platform.
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The density matrix theory of triple-quantum filtered COSY (TQF-COSY) NMR experiments applied to an AX system of spins S=1: An example of passive coupling in two-dimensional NMR Spectroscopy
Concepts in Magnetic Resonance Part A, 2015Co-Authors: Pierre Kempgens, Andrew L. PinchuckAbstract:The 2D Triple-Quantum Filtered (TQF) COSY NMR spectrum of an AX spin system of spin-1 has been calculated by numerical density matrix calculations. The basic phase cycle to achieve triple quantum filtration and phase-modulation of the signal during t1 consists of 12 steps. If nuclei A and X are not coupled, the calculations predict no peaks at all. If nuclei A and X are coupled and the multiplets are not resolved in the conventional 1D spectrum, two diagonal peaks are detected. If nuclei A and X are coupled and the multiplets are resolved in the conventional 1D spectrum, only diagonal and near-diagonal peaks are detected. One does not observe cross peaks if nuclei A and X are coupled because the coupling is passive. It is believed that the calculations presented here will be needed to calculate the Exclusive Correlation Spectroscopy (E.COSY) of an AX system of spins S=1.