Sensitive electrospray mass spectrometry analysis of one-bead-one-compound peptide libraries labeled by quaternary ammonium salts

Bąchor, Remigiusz; Cydzik, Marzena; Kluczyk, Alicja; Stefanowicz, Piotr; Szewczuk, Zbigniew

doi:10.1007/s11030-012-9377-y

Cited by 19 publications

(24 citation statements)

References 26 publications

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“…Recently, we developed a method allowing to obtain peptide conjugates containing N,N,N -trialkyl moieties1516. Although this method was characterized by improved sensitivity of detection, even at the attomole level17, their applicability to peptide sequencing was questionable due to the insufficient stability of linear N,N,N -trialkyl QAS, during MS/MS experiment in view of Hofmann elimination18.…”

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confidence: 99%

Peptides Labeled with Pyridinium Salts for Sensitive Detection and Sequencing by Electrospray Tandem Mass Spectrometry

Waliczek

Kijewska

Setner

et al. 2016

Sci Rep

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Mass spectrometric analysis of trace amounts of peptides may be problematic due to the insufficient ionization efficiency resulting in limited sensitivity. One of the possible ways to overcome this problem is the application of ionization enhancers. Herein we developed new ionization markers based on 2,4,6-triphenylpyridinium and 2,4,6-trimethylpyridinium salts. Using of inexpensive and commercially available pyrylium salt allows selective derivatization of primary amino groups, especially those sterically unhindered, such as ε-amino group of lysine. The 2,4,6-triphenylpyridinium modified peptides generate in MS/MS experiments an abundant protonated 2,4,6-triphenylpyridinium ion. This fragment is a promising reporter ion for the multiple reactions monitoring (MRM) analysis. In addition, the fixed positive charge of the pyridinium group enhances the ionization efficiency. Other advantages of the proposed ionization enhancers are the simplicity of derivatization of peptides and the possibility of convenient incorporation of isotopic labels into derivatized peptides.

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confidence: 99%

Peptides Labeled with Pyridinium Salts for Sensitive Detection and Sequencing by Electrospray Tandem Mass Spectrometry

Waliczek

Kijewska

Setner

et al. 2016

Sci Rep

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“…A resin sample (20 mg) containing PTU-peptide derivative was treated with TFA for 30 min, the solution was evaporated and lyophilized. The remaining resin was treated with CNBr (as described in our previous paper [18]). If the peptide is completely cleaved by PTH formation, in the mass spectrum of the product we should observe only signals corresponding to the Phe-HSL (HSL—homoserine lactone).…”

Section: Resultsmentioning

confidence: 99%

“…Such modification facilitates MS analysis of peptides, allowing for ESI-MS/MS sequencing of trace amounts of compounds by both charge remote and charge directed fragmentation mechanisms [16], even in case of peptides lacking easily mobilizable protons [17]. Our previous work presented the application of QAS for high-throughput analysis of single resin beads from OBOC peptide libraries using high-resolution electrospray ionization tandem mass spectrometry (HR ESI-MS/MS) [18]. The proposed cleavable linker was composed of lysine with the -amino group labeled by QAS and methionine, which allows selective cleavage of the peptide from TentaGel resin by CNBr.…”

Section: Introductionmentioning

confidence: 99%

New method of peptide cleavage based on Edman degradation

et al. 2013

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A straightforward cleavage method for N- acylated peptides based on the phenylthiohydantoin (PTH) formation is presented. The procedure could be applied to acid-stable resins, such as TentaGel HL–NH. We designed a cleavable linker that consists of a lysine residue with the -amino group blocked by Boc, whereas the -amino group is used for peptide synthesis. After the peptide assembly is completed, the protecting groups in peptide side chains are removed using trifluoroacetic acid, thus liberating also the -amino group of the lysine in the linker. Then the reaction with phenyl isothiocyanate followed by acidolysis causes an efficient peptide release from the resin as a stable PTH derivative. Furthermore, the application of a fixed charge tag in the form of 2-(4-aza-1-azoniabicyclo[2.2.2]octylammonium)acetyl group increases ionization efficiency and reduces the detection limit, allowing ESI-MS/MS sequencing of peptides in the subfemtomolar range. The proposed strategy is compatible with standard conditions during one-bead-one-compound peptide library synthesis. The applicability of the developed strategy in combinatorial chemistry was confirmed using a small training library of -chymotrypsin substrates.Electronic supplementary materialThe online version of this article (doi:10.1007/s11030-013-9453-y) contains supplementary material, which is available to authorized users.

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“…The methodology of derivatization of lysine residues by DABCO in peptides on solid support was similar to the one presented by us previously [37]. …”

Section: Methodsmentioning

confidence: 99%

Selective Detection of Carbohydrates and Their Peptide Conjugates by ESI-MS Using Synthetic Quaternary Ammonium Salt Derivatives of Phenylboronic Acids

Kijewska

Kuc

Kluczyk

et al. 2014

J. Am. Soc. Mass Spectrom.

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We present new tags based on the derivatives of phenylboronic acid and apply them for the selective detection of sugars and peptide-sugar conjugates in mass spectrometry. We investigated the binding of phenylboronic acid and its quaternary ammonium salt (QAS) derivatives to carbohydrates and peptide-derived Amadori products by HR-MS and MS/MS experiments. The formation of complexes between sugar or sugar-peptide conjugates and synthetic tags was confirmed on the basis of the unique isotopic distribution resulting from the presence of boron atom. Moreover, incorporation of a quaternary ammonium salt dramatically improved the efficiency of ionization in mass spectrometry. It was found that the formation of a complex with phenylboronic acid stabilizes the sugar moiety in glycated peptides, resulting in simplification of the fragmentation pattern of peptide-derived Amadori products. The obtained results suggest that derivatization of phenylboronic acid as QAS is a promising method for sensitive ESI-MS detection of carbohydrates and their conjugates formed by non-enzymatic glycation or glycosylation.FigureᅟElectronic supplementary materialThe online version of this article (doi:10.1007/s13361-014-0857-4) contains supplementary material, which is available to authorized users.

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Sensitive electrospray mass spectrometry analysis of one-bead-one-compound peptide libraries labeled by quaternary ammonium salts

Cited by 19 publications

References 26 publications

Peptides Labeled with Pyridinium Salts for Sensitive Detection and Sequencing by Electrospray Tandem Mass Spectrometry

Peptides Labeled with Pyridinium Salts for Sensitive Detection and Sequencing by Electrospray Tandem Mass Spectrometry

New method of peptide cleavage based on Edman degradation

Selective Detection of Carbohydrates and Their Peptide Conjugates by ESI-MS Using Synthetic Quaternary Ammonium Salt Derivatives of Phenylboronic Acids

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