Derivatization and mass spectrometric investigations of substituted benzeneboronic acids. The use of linked scanning during gas chromatography mass spectrometry

Longstaff, Colin; Rose, Malcolm E.

doi:10.1002/oms.1210171010

Cited by 23 publications

(15 citation statements)

References 33 publications

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“…26 Conversely, the derivatization of boronic acids with diols and simple sugars to the cyclic boronic esters has proven to reliably eliminate boroxine formation (Figure 2). 17,19,27,28 Indeed, Haas et al demonstrated the successful characterization of small molecular weight boronic ester peptides via positive-ion ammonia chemical ionization (CI) as well as positive-ion LSI-MS. 18 With regards to sequencing peptide boronic acid libraries, Hall has shown that under appropriate conditions, boroxine formation is not necessarily detrimental to library deconvolution. 25 More recently, Leitner and colleagues reported the arginine-specific labeling technique using 2,3-butanedione (BD) and phenylboronic acid (PBA) and subsequent analysis using MALDI-MS. 21 Their work demonstrated that boronic acid-peptide conjugates can be utilized for the identification of peptides based on their mass fingerprint.…”

Section: Introductionmentioning

confidence: 99%

Facile Analysis and Sequencing of Linear and Branched Peptide Boronic Acids by MALDI Mass Spectrometry

2011

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Interest in peptides incorporating boronic acid moieties is increasing due to their potential as therapeutics/diagnostics for a variety of diseases such as cancer. The utility of peptide boronic acids may be expanded with access to vast libraries that can be deconvoluted rapidly and economically. Unfortunately, current detection protocols using mass spectrometry are laborious and confounded by boronic acid trimerization, which requires time consuming analysis of dehydration products. These issues are exacerbated when the peptide sequence is unknown, as with de novo sequencing, and especially when multiple boronic acid moieties are present. Thus, a rapid, reliable and simple method for peptide identification is of utmost importance. Herein, we report the identification and sequencing of linear and branched peptide boronic acids containing up to five boronic acid groups by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Protocols for preparation of pinacol boronic esters were adapted for efficient MALDI analysis of peptides. Additionally, a novel peptide boronic acid detection strategy was developed in which 2,5-dihydroxybenzoic acid (DHB) served as both matrix and derivatizing agent in a convenient, in situ, on-plate esterification. Finally, we demonstrate that DHB-modified peptide boronic acids from a single bead can be analyzed by MALDI-MSMS analysis, validating our approach for the identification and sequencing of branched peptide boronic acid libraries.

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Section: Introductionmentioning

confidence: 99%

Facile Analysis and Sequencing of Linear and Branched Peptide Boronic Acids by MALDI Mass Spectrometry

2011

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“…'-~ In previous studies, we exploited this behaviour to develop a method for structural characterization of substituted aromatic boronic acids, and mixtures thereof, based on a simple derivatization with diols and employing gas ~hromatography,~ direct probe mass spectrometry' and gas chromatography mass spectrometry (GC/MS). 4,5 To extend this work, we now report a novel modification of th6 derivatization procedure for application of fast atom bombardment (FAB) mass spectrometry. 6 The derivatization requires no more than the mixing of a trio1 or analogous compound of appropriate configuration and a boronic acid on the probe tip of the FAB instrument.…”

Section: Introductionmentioning

confidence: 99%

Negative ion fast atom bombardment mass spectrometry.In situreactions of boronic acids with triols and related compounds, sugars and nucleosides

Rose

Longstaff

Dean

1983

Biol. Mass Spectrom.

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On the probe tip of a fast atom bombardment mass spectrometer, boronic acids react with a wide range of trifunctional compounds of appropriate configuration yielding negatively-charged boronate cage compounds. Formation of 5-to 8-membered rings occurs readily in the mass spectrometer. The reaction constitutes a simple and effective means of pre-ionizing boronic acids, triols, aminodiols, monomercaptodiols and related compounds including sugars and nucleosides. The resulting boronate complexes exhibit excellent negative ion fast atom bombardment mass spectra, indicating wide application for (1) analysing polyhydroxy compounds and boronic acids, (2) providing information on configuration of polyhydroxy compounds, and (3) measuring affinity constants of polyfunctional compounds for boronic acids. The use of polyethylene glycol as solvent and mass calibrant is also discussed.

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“…HRMS for compound 4 was determined as the pinacol ester via derivatization with 2,3-dimethyl butane diol. 53…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Antimicrobial Evaluation of γ-Borono Phosphonate Compounds in Escherichia coli and Mycobacterium smegmatis

et al. 2019

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Drug resistance in bacteria is a serious threat, and drugs with novel modes of action are constantly needed. Fosmidomycin is a naturally occurring antibiotic that inhibits the nonmevalonate pathway via inhibition of the enzyme 1-deoxylulose-5-phosphate reductoisomerase (DXR). This work is the first report in which a boronic acid is evaluated as an isostere of the retrohydroxamate moiety of fosmidomycin. We report the novel synthesis of a γ-borono phosphonate analog of fosmidomycin and its corresponding prodrugs. We evaluate the inhibition of DXR and the antimicrobial activity of γ-borono phosphonate compounds against Escherichia coli wild type, E. coli Δglycerol-3-phosphate transporter, and Mycobacterium smegmatis. Despite its structural similarities, the γ-borono phosphonate compound shows antimicrobial activity against E. coli with a mechanism of action that is different from fosmidomycin. This was proven with an underutilized method for studying in vitro inhibition of the MEP pathway in E. coli via isopentenyl pyrophosphate chemical rescue. These results indicate that these compounds may serve as a promising scaffold for developing a new class of antimicrobial agents.

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Derivatization and mass spectrometric investigations of substituted benzeneboronic acids. The use of linked scanning during gas chromatography mass spectrometry

Cited by 23 publications

References 33 publications

Facile Analysis and Sequencing of Linear and Branched Peptide Boronic Acids by MALDI Mass Spectrometry

Facile Analysis and Sequencing of Linear and Branched Peptide Boronic Acids by MALDI Mass Spectrometry

Negative ion fast atom bombardment mass spectrometry.In situreactions of boronic acids with triols and related compounds, sugars and nucleosides

Synthesis and Antimicrobial Evaluation of γ-Borono Phosphonate Compounds in Escherichia coli and Mycobacterium smegmatis

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