Analysis of Solid-Phase Reactions: Product Identification and Quantification by Use of UV-Chromophore-Containing Dual-Linker Analytical Constructs

Williams, Geoffrey Lee; Carr, Robin A. E.; Congreve, Miles; Kay, Corinne; McKeown, Stephen C.; Murray, Peter; Scicinski, Jan; Watson, Steve P.

doi:10.1002/1521-3773(20000915)39:18<3293::aid-anie3293>3.0.co;2-b

Cited by 26 publications

(21 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since Merrifield and Tam first introduced the concept of “multidetachable” resins as early as 1979 [ 13 , 14 ], dozens of similar studies have been published [ 15 , 16 , 17 , 18 , 19 ]. Among these, a technique, named “analytical construct”, for solid phase reaction monitoring has been developed by Geysen et al [ 20 ] and attracted much attention [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. The construct typically comprises two selective-cleavable in-line linkers, involving a MS sensitizer (usually an amine) which can greatly improve the ionization properties of the materials and thus allowing easy detection by electrospray mass spectrometry [ 31 ] and a MS splitter which is an isotope label giving rise to a characteristic split-peak pattern in MS [ 20 , 32 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of a Dual Linker for Solid Phase Synthesis of Oleanolic Acid Derivatives

Wang

Fang

2011

Molecules

View full text Add to dashboard Cite

A hydrophilic amino-terminated poly(ethylene glycol)-type dual linker for solid phase synthesis of oleanolic acid derivatives using trityl chloride resin was designed and synthesized for the first time. Model reactions in both liquid and solid phase were performed to show the feasibility of its selective cleavage at two different sites. The biological assay results indicated that the long and flexible alkyl ether functionality in the linker is less likely to be critical for the binding event. Following the successful solid-phase synthesis of model compounds, the potential of this dual linker in reaction monitoring and target identification is deemed worthy of further study.

show abstract

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of a Dual Linker for Solid Phase Synthesis of Oleanolic Acid Derivatives

Wang

Fang

2011

Molecules

View full text Add to dashboard Cite

show abstract

“…Our group has developed optical assays for enantiomeric excess (ee) that involve molecular recognition or multicomponent assemblies. ,, Circular dichroism (CD) signal that arise upon binding of a chiral analyte are correlated to the sample’s ee values through experimentally derived calibration curves. To date, efforts to generate structure–activity predictive models have been primarily focused upon UV and fluorescence spectra of small organic molecules or assembly. ,− Doing so with the CD spectra generated from our chiral sensing systems would remove the necessity to generate a calibration curve for every unique chiral analyte prior to analysis.…”

mentioning

confidence: 99%

Model Building Using Linear Free Energy Relationship Parameters–Eliminating Calibration Curves for Optical Analysis of Enantiomeric Excess

2016

View full text Add to dashboard Cite

Linear free energy relationship (LFER) parameters are routinely used to parametrize physicochemical effects while investigating reaction mechanisms. In this Communication, we describe an alternate application for LFERs: training sets for model building in an analytical application. In this study, the sterics, quantified by Charton parameters (Δv), of nine secondary chiral alcohol analytes were correlated to the circular dichroism output from a chiral alcohol optical sensor. To test the validity of the model, the correlative linear model was applied to determine the enantiomeric excess of samples of two alcohols without a priori knowledge of a calibration curve. The error in this method was comparable to those of previous experimental methods (<5%).

show abstract

“…To do this, groups have tried to level the ionisation coefficients by incorporating an arginine amino acid distant from the cleavage site 34. Quantitation could also be achieved by incorporating a unique UV chromophore within the molecule 39…”

Section: Discussionmentioning

confidence: 99%

Differential isotopic mass splitting as a mass spectrometric tool for identifying protease substrates

McKeown

Heudi

Kay

et al. 2002

Rapid Comm Mass Spectrometry

Self Cite

View full text Add to dashboard Cite

A method is described whereby stable isotopic signatures were partially incorporated into both termini of a peptide sequence giving rise to a characteristic cluster of four peaks in the mass spectral analysis. Cleavage of this peptide by a protease between the labeled positions generates two fragments both displaying their own individual signature peaks. The event of protease cleavage of the peptide was monitored by the changes in clusters within the spectrum. We believe that this technique could be used to aid the discovery of new cleavage substrates for proteases. Additionally, the analysis can be automated with dedicated software designed to select and interpret the data since all peaks of interest contain predefined signatures and can be easily distinguished from background noise.

show abstract

Analysis of Solid-Phase Reactions: Product Identification and Quantification by Use of UV-Chromophore-Containing Dual-Linker Analytical Constructs

Cited by 26 publications

References 9 publications

Design and Synthesis of a Dual Linker for Solid Phase Synthesis of Oleanolic Acid Derivatives

Design and Synthesis of a Dual Linker for Solid Phase Synthesis of Oleanolic Acid Derivatives

Model Building Using Linear Free Energy Relationship Parameters–Eliminating Calibration Curves for Optical Analysis of Enantiomeric Excess

Differential isotopic mass splitting as a mass spectrometric tool for identifying protease substrates

Contact Info

Product

Resources

About