Prediction of retention for sulfonamides in supercritical fluid chromatography

Cazenave-Gassiot, Amaury; Boughtflower, Robert J.; Caldwell, Jeffrey; Coxhead, Richard; Hitzel, Laure; Lane, Stephen; Oakley, Paul; Holyoak, Clare; Pullen, Frank S.; Langley, G. John

doi:10.1016/j.chroma.2007.10.020

Cited by 12 publications

(3 citation statements)

References 26 publications

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“…Instead, a dipole-dipole or charge-dipole interaction may occur. The amide nitrogen of a polypeptide supports at least a partial positive charge (54), which would interact with the strongly electronegative sulfonamide oxygen (55). Interestingly, both the dimeric biarylsulfonamide (30) and LY404187 (8), other members of the full spanning modulator class, also have a sulfonamide that interacts with the same backbone atoms of P494 and G731 as PEPA (Figure 4C).…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of Flop Selectivity and Subsite Recognition for an AMPA Receptor Allosteric Modulator: Structures of GluA2 and GluA3 in Complexes with PEPA

2010

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Glutamate receptors are important potential drug targets for cognitive enhancement and the treatment of schizophrenia in part because they are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system. One approach to the application of therapeutic agents to the AMPA subtype of glutamate receptors is the use of allosteric modulators, which promote dimerization by binding to a dimer interface thereby reducing desensitization and deactivation. AMPA receptors exist in two alternatively spliced variants (flip and flop) that differ in desensitization and receptor activation profiles. Most of the structural information on modulators of the AMPA receptor target the flip subtype. We report here the crystal structure of the flop-selective allosteric modulator, PEPA, bound to the binding domains of the GluA2 and GluA3 flop isoforms of AMPA receptors. Specific hydrogen bonding patterns can explain the preference for the flop isoform. This includes a bidentate hydrogen bonding pattern between PEPA and N754 of the flop isoforms of GluA2 and GluA3 (the corresponding position in the flip isoform is S754). Comparison with other allosteric modulators provides a framework for the development of new allosteric modulators with preferences for either the flip or flop isoforms. In addition to interactions with N/S754, specific interactions of the sulfonamide with conserved residues in the binding site are characteristics of a number of allosteric modulators. These, in combination, with variable interactions with five subsites on the binding surface lead to different stoichiometries, orientations within the binding pockets, and functional outcomes.

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Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of Flop Selectivity and Subsite Recognition for an AMPA Receptor Allosteric Modulator: Structures of GluA2 and GluA3 in Complexes with PEPA

2010

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“…Retention characteristics of sulfonamides were calculated (79). Literature studies of quantitative structure-retention relationships showed that these characteristics can be correlated with simple molecular descriptors to derive equations predicting the retention behavior of new compounds.…”

Section: Methods Developmentmentioning

confidence: 99%

Supercritical Fluid Chromatography

Taylor

2010

Anal. Chem.

123

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“…Supercritical fluid chromatography (SFC) can be considered as a normal‐phase chromatography option and it has been used in the mass spectrometry research group at the University of Southampton, Chemistry since 2004. A Berger SFC™ Minigram (Mettler Toledo, Greifensee, Switzerland) was used to predict the retention behaviour of pharmaceutical compounds and investigate the performance of ammonium acetate as an additive to the modifier . Experience and knowledge in this field of chromatography, particularly in the coupling to mass spectrometry, made the introduction of UHPSFC/MS to the open access facility an obvious approach.…”

Section: University Of Southampton Chemistry Mass Spectrometrymentioning

confidence: 99%

Open Access UHPSFC/MS – an additional analytical resource for an academic mass spectrometry facility

Herniman

Langley

2016

Rapid Comm Mass Spectrometry

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RATIONALE:Many compounds submitted for analysis in Chemistry at the University of Southampton do not retain, elute or ionize using open access reversed-phase ultra-high-performance liquid chromatography/mass spectrometry (RP-UHPLC/MS) and require analysis via infusion. An ultra-high-performance supercritical fluid chromatography mass spectrometry approach was implemented to afford high-throughput analysis of these compounds with chromatographic separation. METHODS: A UPC 2 -TQD MS system has been incorporated into the open access MS provision within Chemistry at the University of Southampton, using an ESCi source (electrospray and atmospheric pressure chemical ionization) and an atmospheric pressure photoionization (APPI) source. Access to instrumentation is enabled via a web-based interface (RemoteAnalyzer ™ ). RESULTS: Compounds such as fluorosugars, fullerenes, phosphoramidites, porphyrins, and rotaxanes exhibiting properties incompatible with RP-UHPLC/MS have been analyzed using automated chromatography and mass spectrometry methods. The speedy return of data enables research in these areas to progress unhindered by sample type. The provision of an electronic web format enables easy incorporation of chromatograms and mass spectra into electronic files and reports. CONCLUSIONS: The implementation of UHPSFC/MS increases access to a wide range of chemistries incompatible with reversed-phase chromatography and polar solvents, enabling more than 90% of submitted samples to be analyzed using an open access approach. Further, chromatographic separation is provided where previously flow injection or infusion analyses were the only options.

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Prediction of retention for sulfonamides in supercritical fluid chromatography

Cited by 12 publications

References 26 publications

Molecular Mechanism of Flop Selectivity and Subsite Recognition for an AMPA Receptor Allosteric Modulator: Structures of GluA2 and GluA3 in Complexes with PEPA

Molecular Mechanism of Flop Selectivity and Subsite Recognition for an AMPA Receptor Allosteric Modulator: Structures of GluA2 and GluA3 in Complexes with PEPA

Supercritical Fluid Chromatography

Open Access UHPSFC/MS – an additional analytical resource for an academic mass spectrometry facility

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