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MALDI In-Source Decay, from Sequencing to Imaging

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Applications of MALDI-TOF Spectroscopy

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 331))

Abstract

Matrix-assisted laser desorption/ionization (MALDI) is now a mature method allowing the identification and, more challenging, the quantification of biopolymers (proteins, nucleic acids, glycans, etc). MALDI spectra show mostly intact singly charged ions. To obtain fragments, the activation of singly charged precursors is necessary, but not efficient above 3.5 kDa, thus making MALDI MS/MS difficult for large species. In-source decay (ISD) is a prompt fragmentation reaction that can be induced thermally or by radicals. As fragments are formed in the source, precursor ions cannot be selected; however, the technique is not limited by the mass of the analyzed compounds and pseudo MS3 can be performed on intense fragments. The discovery of new matrices that enhance the ISD yield, combined with the high sensitivity of MALDI mass spectrometers, and software development, opens new perspectives. We first review the mechanisms involved in the ISD processes, then discuss ISD applications like top-down sequencing and post-translational modifications (PTMs) studies, and finally review MALDI-ISD tissue imaging applications.

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Abbreviations

2-AA:

Anthranilic acid

2-AB:

2-Aminobenzamide

5-ASA:

5-Aminosalicylic acid

ATT:

6-Aza-2-thiothymine

BLAST:

Basic Local Alignment Search Tool

CHCA:

α-Cyanohydroxycinnamic acid

CID:

Collision induced dissociation

1,5-DAN:

1,5-Diaminonaphthalene

2,5-DHB:

2,5-Dihydroxybenzoic acid

ECD:

Electron capture dissociation

ED:

Edman degradation

ETD:

Electron transfer dissociation

(HP)LC:

High performance liquid chromatography

ISD:

In-source decay

MALDI:

Matrix-assisted laser desorption/ionization

MS/MS:

Tandem mass spectrometry

PMF:

Peptide-mass fingerprinting

PSD:

Post-source decay

PTM:

Post-translational modification

TDS:

Top-down sequencing

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Acknowledgments

The F.R.S.-FNRS (Fonds National de la Recherche Scientifique, Belgium) is acknowledged for postdoctoral fellowships to D.D., T.A.Z., and N.S. The Japanese Society for the Promotion of Science is acknowledged for the postdoctoral fellowship of D.A. The instrumentation was funded by the FNRS, The University of Liege, and the FEDER funds.

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Correspondence to Edwin De Pauw .

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Debois, D. et al. (2012). MALDI In-Source Decay, from Sequencing to Imaging. In: Cai, Z., Liu, S. (eds) Applications of MALDI-TOF Spectroscopy. Topics in Current Chemistry, vol 331. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2012_363

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