De novo sequencing of peptides on single resin beads by MALDI-FTICR tandem mass spectrometry.

Journal of the American Society for Mass Spectrometry
Angelika SemmlerValentin Wittmann

Abstract

An efficient approach in combinatorial chemistry is the synthesis of one-bead-one-compound peptide libraries. In contrast to synthesis and functional screening, which is performed in a largely automated manner, structure determination has been frequently laborious and time-consuming. Here we report an approach for de novo sequencing of peptides on single beads by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance (MALDI-FTICR) tandem mass spectrometry, using a resin with a photolinker for solid-phase peptide synthesis. Upon sorting out single beads, an efficient sample preparation on the MALDI target was developed that enables fragmentation upon irradiation of the bead-matrix mixture with the ultraviolet (UV)-MALDI laser, with enhanced yield of sequence-specific fragment ions at increased laser energy. This approach is illustrated by sequence determinations of two peptides from a library with sequences varying in a single amino acid; the feasibility with tandem-MS procedures and fragment ion assignment was ascertained by sustained off-resonance irradiation/collision induced dissociation (SORI/CID) and infrared multiphoton dissociation (IRMPD) fragmentation.

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Citations

Apr 18, 2013·Rapid Communications in Mass Spectrometry : RCM·David Gode, Dietrich A Volmer
Apr 22, 2017·Journal of Mass Spectrometry : JMS·F M Nachtigall, L S Santos
Jun 12, 2018·Chemical Communications : Chem Comm·Vitaly V KomnatnyyKatrine Qvortrup
Jul 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniela KalafatovicErnest Giralt
Mar 2, 2021·Chemical Communications : Chem Comm·Suan TuangBradley L Pentelute
Jan 20, 2011·Bioconjugate Chemistry·Frank ThielbeerMark Bradley
Sep 12, 2017·ACS Combinatorial Science·Alexander A VinogradovBradley L Pentelute

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