Investigation of monovalent and bivalent enantioselective molecular recognition by electrospray ionization-mass spectrometry and tandem mass spectrometry

Schug, Kevin A.; Joshi, Manishkumar D.; Fryčák, Petr; Maier, Norbert M.; Lindner, Wolfgang

doi:10.1016/j.jasms.2008.07.010

Cited by 11 publications

(3 citation statements)

References 74 publications

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“…Specifically, for the protonated monoanionic system, the solvent can be assumed to play a minor role relative to the stereochemical orientation of the associates in providing enantioselective binding. In other words, solvation is not necessarily needed to maintain a delicate balance of noncovalent forces, contrary to that shown for other enantioselective systems [25]. Further studies incorporating different solution conditions (% organic, pH, and ionic strength) are needed to confirm this assertion.…”

Section: Th Values (mentioning

confidence: 89%

Antimony(III)-D, L-tartrates exhibit proton-assisted enantioselective binding in solution and in the gas phase

Wijeratne

Miko

Gracia

et al. 2009

J. Am. Soc. Mass Spectrom.

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The negative ion mode ESI mass spectral analysis of antimony(III)-D-and -L-tartrate ("tartar emetic"), in association with leucine enantiomeric isotopomers, revealed remarkable protonassisted enantioselective molecular recognition phenomena. The current study infers that recognition of amino acids by antimony(III)-D,L-tartrate complexes requires that the chiral selector associate a proton to become enantioselective. The dianionic selector itself failed to show enantiomeric discrimination capacity. This observation was shown to be consistent both in solution-phase targeting full scan and gas-phase targeting collision threshold dissociation (CTD) experiments. Importantly, this disparity in enantioselective binding capacity between the dianionic and the protonated monoanionic representatives of antimony(III)-D-and -L-tartrates could only be clearly revealed by ESI-MS and tandem mass spectrometry experiments as described herein. This finding urges a more in-depth study of mechanisms associated with exhibited enantiomeric resolving capacity of antimony tartrates in HPLC and CE applications, as well as in former ESI-MS association studies. (J Am Soc Mass Spectrom 2009, 20, 2100 -2105

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Section: Th Values (mentioning

confidence: 89%

Antimony(III)-D, L-tartrates exhibit proton-assisted enantioselective binding in solution and in the gas phase

Wijeratne

Miko

Gracia

et al. 2009

J. Am. Soc. Mass Spectrom.

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“…Hereby, the binding intensity between the target protein and a newly developed inhibitor molecule is of central interest. In recent years, very promising efforts have been made to deduce the binding constant of an inhibitor from its fragmentation behavior in MS [4][5][6][7][8][9][10][11][12]. For instance, Rogniaux et al published a method to determine binding constants of aldose reductase inhibitors from the accelerating cone voltage in the MS interface region, which was required to dissociate 50% of the complex (Vc 50 ) [4].…”

Section: Introductionmentioning

confidence: 99%

CE‐ESI‐MS/MS as a rapid screening tool for the comparison of protein–ligand interactions

Hoffmann

Martin

2010

Electrophoresis

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In drug development, the combinatorial synthesis of drug libraries is common use, therefore efficient tools for the characterization of drug candidates and the extent of interaction between a drug and its target protein is a central question of analytical interest. While biological activity is tested today by enzyme assays, MS techniques attract more and more attention as an alternative for a rapid comparison of drug-target interactions. CE enables the separation of proteins and drug-enzyme complexes preserving their physiological activity in aqueous media. By hyphenating CE with ESI-MS/MS, the binding strength of enzyme inhibitors can be deduced from MS/MS experiments, which selectively release the inhibitor from the drug-target complex after CID. In this study, alpha-chymotrypsin (CT), a serine protease, was chosen as a model compound. Chymostatin is a naturally occurring peptide aldehyde binding to CT through a hemiacetal bond and electrostatic interaction. First, a CE separation was developed, which allows the analysis of alpha-CT and a chymotrypsin-chymostatin complex under MS-compatible conditions. The use of neutral-coated CE capillaries was mandatory to reduce analyte-wall interactions. ESI-quadrupole ion trap-MS was worked out to demonstrate the selective drug release after CID. Fragmentation of the drug-enzyme complex was monitored in dependence from the excitation energy in the ion trap, leading to the V(50) voltage that enables 50% complex fragmentation as a reference value for chymotrypsin-chymostatin complex. A stable CE-ESI-MS/MS setup was established, which preserves the drug-enzyme complexes during ionization-desolvation processes. With this optimized setup, different CT inhibitors could be investigated and compared.

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“…In practice, such correlation can be systemdependent and should be rigorously examined. Gas phase intermolecular interaction studies in MS are also common [61,62], having been carried out by different methods, including collisional dissociation of diastereomeric complexes [63], the kinetic method [64], ion-molecule guest-exchange reactions [65,66], and a variety of other more complicated set-ups [67,68]. In these studies, while enantioselective interactions can be investigated directly in the absence of solvent, this also provides a drawback regarding the formulation of conclusions with respect to solvent-dependent recognition mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Molecular recognition properties of tartrates and metal‐tartrates in solution and gas phase

Wijeratne

Schug²

2009

J of Separation Science

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Investigation of monovalent and bivalent enantioselective molecular recognition by electrospray ionization-mass spectrometry and tandem mass spectrometry

Cited by 11 publications

References 74 publications

Antimony(III)-D, L-tartrates exhibit proton-assisted enantioselective binding in solution and in the gas phase

Antimony(III)-D, L-tartrates exhibit proton-assisted enantioselective binding in solution and in the gas phase

CE‐ESI‐MS/MS as a rapid screening tool for the comparison of protein–ligand interactions

Molecular recognition properties of tartrates and metal‐tartrates in solution and gas phase

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