DOTA based metal labels for protein quantification: a review

Schwarz, Gunnar; Mueller, Larissa; Beck, Sebastian; Linscheid, Michael

doi:10.1039/c3ja50277e

Cited by 69 publications

(66 citation statements)

References 89 publications

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“…Although relatively small, the size and flexibility of the tethering DOTA arm appeared to outweigh the contribution from the pseudosecular term of the dipolar coupling Hamiltonian during Tikhonov regularization analysis. These advantages can potentially be further exploited by affixing MnDOTA to the biomolecule of interest in a more constrained manner, for example, by using 2,2′,2′′‐(10‐{2‐[(2,5‐dioxopyrrolidin‐1‐yl)oxy]‐2‐oxoethyl}‐1,4,7,10‐tetraazacyclododecane‐1,4,7‐triyl)triacetic acid (DOTA‐NHS ester), the protein backbone can be directly labeled at the N terminus, or by using a derivative with short thiol‐reactive tethers, similar to the Gd III complexes very recently reported by Abdelkader et al …”

Section: Discussionmentioning

confidence: 99%

A Bis‐Manganese(II)–DOTA Complex for Pulsed Dipolar Spectroscopy

et al. 2016

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High-spin gadolinium(III) and manganese(II) complexes have emerged as alternatives to standard nitroxide radical spin labels for measuring nanometric distances by using pulsed electron-electron double resonance (PELDOR or DEER) at high fields/frequencies. For certain complexes, particularly those with relatively small zero-field splitting (ZFS) and short distances between the two metal centers, the pseudosecular term of the dipolar coupling Hamiltonian is non-negligible. However, in general, the contribution from this term during conventional data analysis is masked by the flexibility of the molecule of interest and/or the long tethers connecting them to the spin labels. The efficient synthesis of a model system consisting of two [Mn(dota)](2-) (MnDOTA; DOTA(4-) =1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) directly connected to the ends of a central rodlike oligo(phenylene-ethynylene) (OPE) spacer is reported. The rigidity of the OPE is confirmed by Q-band PELDOR measurements on a bis-nitroxide analogue. The Mn(II) -Mn(II) distance distribution profile determined by W-band PELDOR is in reasonable agreement with one simulated by using a simple rotamer analysis. The small degree of flexibility arising from the linking MnDOTA arm appears to outweigh the contribution from the pseudosecular term at this interspin distance. This study illustrates the potential of MnDOTA-based spin labels for measuring fairly short nanometer distances, and also presents an interesting candidate for in-depth studies of pulsed dipolar spectroscopy methods on Mn(II) -Mn(II) systems.

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Section: Discussionmentioning

confidence: 99%

A Bis‐Manganese(II)–DOTA Complex for Pulsed Dipolar Spectroscopy

et al. 2016

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“…A, Tags containing more than one metal ion for increased sensitivity. B, Different tags with distinct reactivity for functional groups for quantitative differentiation of the targeted groups or the same metal ion to increase sensitivity…”

Section: Labelingmentioning

confidence: 99%

“…In analogy to iTRAQ, approaches were developed for tags carrying a metal, such as silicon, mercury, or iron . Several reviews discuss the recent developments . Especially labeling with lanthanoide complexes showed great potential due to their excellent detection limits with ICP‐MS and their low biological background .…”

Section: Introductionmentioning

confidence: 99%

Molecules and elements for quantitative bioanalysis: The allure of using electrospray, MALDI, and ICP mass spectrometry side‐by‐side

Linscheid

2018

Mass Spectrometry Reviews

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To understand biological processes, not only reliable identification, but quantification of constituents in biological processes play a pivotal role. This is especially true for the proteome: protein quantification must follow protein identification, since sometimes minute changes in abundance tell the real tale. To obtain quantitative data, many sophisticated strategies using electrospray and MALDI mass spectrometry (MS) have been developed in recent years. All of them have advantages and limitations. Several years ago, we started to work on strategies, which are principally capable to overcome some of these limits. The fundamental idea is to use elemental signals as a measure for quantities. We began by replacing the radioactive P with the "cold" natural P to quantify modified nucleotides and phosphorylated peptides and proteins and later used tagging strategies for quantification of proteins more generally. To do this, we introduced Inductively Coupled Plasma Mass Spectrometry (ICP-MS) into the bioanalytical workflows, allowing not only reliable and sensitive detection but also quantification based on isotope dilution absolute measurements using poly-isotopic elements. The detection capability of ICP-MS becomes particularly attractive with heavy metals. The covalently bound proteins tags developed in our group are based on the well-known DOTA chelate complex (1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid) carrying ions of lanthanoides as metal core. In this review, I will outline the development of this mutual assistance between molecular and elemental mass spectrometry and discuss the scope and limitations particularly of peptide and protein quantification. The lanthanoide tags provide low detection limits, but offer multiplexing capabilities due to the number of very similar lanthanoides and their isotopes. With isotope dilution comes previously unknown accuracy. Separation techniques such as electrophoresis and HPLC were used and just slightly adapted workflows, already in use for quantification in bioanalysis. Imaging mass spectrometry (MSI) with MALDI and laser ablation ICP-MS complemented the range of application in recent years.

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“…The recent challenges in quantitative proteomics have prompted the development of approaches to solve issues in sensitivity and dynamic range that limit the current stable isotope labeling methods with ESI‐ or MALDI‐MS. Thus, metal‐containing labels with 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA)‐based complexes have been developed which allow to use the high sensitivity, wide dynamic range and multi‐elemental capabilities of ICP‐MS for quantification of biomolecules . In the last years, many studies using metal‐coded affinity tags (MeCAT) have been published targeting cysteine residues in peptides and proteins.…”

Section: Introductionmentioning

confidence: 99%

Application of higher energy collisional dissociation (HCD) to the fragmentation of new DOTA‐based labels and N‐termini DOTA‐labeled peptides

El‐Khatib

Esteban-Fernández

et al. 2017

J. Mass Spectrom.

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1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivatives are applied in quantitative proteomics owing to their ability to react with different functional groups, to harbor lanthanoides and hence their compatibility with molecular and elemental mass spectrometry. The new DOTA derivatives, namely Ln-MeCAT-Click and Ln-DOTA-Dimedone, allow efficient thiol labeling and targeting sulfenation as an important post-translational modification, respectively. Quantitative applications require the investigation of fragmentation behavior of these reagents. Therefore, the fragmentation behavior of Ln-MeCAT-Click and Ln-DOTA-Dimedone was studied using collision-induced dissociation (CID), infrared multiphoton dissociation (IRMPD) and higher-energy collision dissociation (HCD) using different energy levels, and the efficiency of reporter ion production was estimated. The efficiency of characteristic fragment formation was in the order IRMPD > HCD (normal energy level) > CID. On the other hand, the application of HCD at high energy levels (HCD@HE; NCE > 250%) resulted in a significant increase in reporter ion production (33-54%). This new strategy was successfully applied to generate label-specific reporter ions for DOTA amino labeling at the N-termini and in a quantitative fashion for the estimation of amino:thiol ratio in peptides. Copyright © 2017 John Wiley & Sons, Ltd.

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DOTA based metal labels for protein quantification: a review

Cited by 69 publications

References 89 publications

A Bis‐Manganese(II)–DOTA Complex for Pulsed Dipolar Spectroscopy

A Bis‐Manganese(II)–DOTA Complex for Pulsed Dipolar Spectroscopy

Molecules and elements for quantitative bioanalysis: The allure of using electrospray, MALDI, and ICP mass spectrometry side‐by‐side

Application of higher energy collisional dissociation (HCD) to the fragmentation of new DOTA‐based labels and N‐termini DOTA‐labeled peptides

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