We report on a detailed NMR spectroscopic study of the catalyst-substrate interaction of a highly enantioselective oligopeptide catalyst that is used for the kinetic resolution of trans-cycloalkane-1,2-diols via monoacylation. The extraordinary selectivity has been rationalized by molecular dynamics as well as density functional theory (DFT) computations. Herein we describe the conformational analysis of the organocatalyst studied by a combination of nuclear Overhauser effect (NOE) and residual dipolar coupling (RDC)-based methods that resulted in an ensemble of four final conformers. To corroborate the proposed mechanism, we also investigated the catalyst in mixtures with both trans-cyclohexane-1,2-diol enantiomers separately, using advanced NMR methods such as T1 relaxation time and diffusion-ordered spectroscopy (DOSY) measurements to probe molecular aggregation. We determined intramolecular distance changes within the catalyst after diol addition from quantitative NOE data. Finally, we developed a pure shift EASY ROESY experiment using PSYCHE homodecoupling to directly observe intermolecular NOE contacts between the trans-1,2-diol and the cyclohexyl moiety of the catalyst hidden by spectral overlap in conventional spectra. All experimental NMR data support the results proposed by earlier computations including the proposed key role of dispersion interaction.Mission possible: Advanced NMR spectroscopic data support the mechanism proposed for a highly enantioselective acylation reaction. The pocket-like structure of the catalyst is structurally affected upon the addition of the preferentially acetylated diol substrate and key dispersion interactions between catalyst and substrate were uncovered by a newly developed pure shift EASY ROESY experiment.
[NMR paper] Advanced solid-state NMR techniques for characterization of membrane protein structure and dynamics: Application to Anabaena Sensory Rhodopsin.
Advanced solid-state NMR techniques for characterization of membrane protein structure and dynamics: Application to Anabaena Sensory Rhodopsin.
Related Articles Advanced solid-state NMR techniques for characterization of membrane protein structure and dynamics: Application to Anabaena Sensory Rhodopsin.
J Magn Reson. 2014 Dec 26;
Authors: Ward ME, Brown LS, Ladizhansky V
Abstract
Studies of the structure, dynamics, and function of membrane proteins (MPs) have long been considered one of the main applications of solid-state...
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[NMR paper] Advanced Solid-State NMR Techniques for Characterization of Membrane Protein Structure and Dynamics: Application to Anabaena Sensory Rhodopsin
Advanced Solid-State NMR Techniques for Characterization of Membrane Protein Structure and Dynamics: Application to Anabaena Sensory Rhodopsin
Publication date: Available online 26 December 2014
Source:Journal of Magnetic Resonance</br>
Author(s): Meaghan E. Ward , Leonid S. Brown , Vladimir Ladizhansky</br>
Studies of the structure, dynamics, and function of membrane proteins (MPs) have long been considered one of the main applications of solid-state NMR (SSNMR). Advances in instrumentation, and the plethora of new SSNMR methodologies developed over the past...
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[NMR paper] NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.
NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-2250-98-WileyOnlineLibrary-Button_120x27px_FullText.gif Related Articles NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.
J Pept Sci. 2013 Jan;19(1):33-45
Authors: Rawat A, Kumar D
...
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[NMR paper] Refinement of NMR structures using implicit solvent and advanced sampling techniques.
Refinement of NMR structures using implicit solvent and advanced sampling techniques.
Related Articles Refinement of NMR structures using implicit solvent and advanced sampling techniques.
J Am Chem Soc. 2004 Dec 15;126(49):16038-47
Authors: Chen J, Im W, Brooks CL
NMR biomolecular structure calculations exploit simulated annealing methods for conformational sampling and require a relatively high level of redundancy in the experimental restraints to determine quality three-dimensional structures. Recent advances in generalized Born (GB)...
[NMR paper] Proton NMR and structural features of a 24-nucleotide RNA hairpin.
Proton NMR and structural features of a 24-nucleotide RNA hairpin.
Related Articles Proton NMR and structural features of a 24-nucleotide RNA hairpin.
Biochemistry. 1995 May 16;34(19):6488-503
Authors: Borer PN, Lin Y, Wang S, Roggenbuck MW, Gott JM, Uhlenbeck OC, Pelczer I
The three-dimensional conformation of a 24-nucleotide variant of the RNA binding sequence for the coat protein of bacteriophage R17 has been analyzed using NMR, molecular dynamics, and energy minimization. The imino proton spectrum is consistent with base pairing...
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[NMR paper] Some structural features of cluster-coordinating cysteines of Clostridium pasteurianu
Some structural features of cluster-coordinating cysteines of Clostridium pasteurianum ferredoxin are revealed by 2D TOCSY 1H NMR on the oxidized protein.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles Some structural features of cluster-coordinating cysteines of Clostridium pasteurianum ferredoxin are revealed by 2D TOCSY 1H NMR on the oxidized protein.
Biochem Biophys Res Commun. 1994 Jul 15;202(1):591-5
Authors: Acquotti D, Bonomi F, Brocca P, Ganadu ML, Pagani S
...
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Precise structural determination of weakly binding peptides by utilizing dihedral ang
Abstract Structural determination of target-bound conformations of peptides is of primary importance for the optimization of peptide ligands and peptideā??mimetic design. In the structural determination of weakly binding ligands, transferred nuclear Overhauser effect (TrNOE) methods have been widely used. However, not many distance constraints can be obtained from small peptide ligands by TrNOE, especially for peptides bound to a target molecule in an extended conformation. Therefore, for precise structural determination of weakly binding peptides, additional structural constraints are...
Uncovering Key Structural Features of an Enantioselective Peptide-Catalyzed Acylation Utilizing Advanced NMR Techniques
Linear Mode
