Identification of Isomeric N-Glycans by Conformer Distribution Fingerprinting using Ion Mobility Mass Spectrometry
| Autor: | Sastre Toraño, Javier, Aizpurua-Olaizola, Oier, Wei, Na, Li, Tiehai, Unione, Luca, Jiménez-Osés, Gonzalo, Corzana, Francisco, Somovilla, Victor J, Falcon-Perez, Juan M, Boons, Geert-Jan, Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery |
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| Rok vydání: | 2020 |
| Předmět: |
Glycan
Ion-mobility spectrometry carbohydrates 010402 general chemistry Mass spectrometry Branching (polymer chemistry) 01 natural sciences Catalysis Mass Spectrometry Ion Molecular dynamics Computational chemistry ion mobility spectrometry Conformational isomerism chemistry.chemical_classification biology Full Paper 010405 organic chemistry Chemistry Biomolecule Organic Chemistry General Chemistry Full Papers molecular dynamics 0104 chemical sciences biology.protein conformations chemo-enzymatic synthesis |
| Zdroj: | Chemistry (Weinheim an Der Bergstrasse, Germany) Chemistry-A European Journal, 27(6), 2149. Wiley RIUR. Repositorio Institucional de la Universidad de La Rioja instname |
| ISSN: | 1521-3765 0947-6539 |
| Popis: | Glycans possess unparalleled structural complexity arising from chemically similar monosaccharide building blocks, configurations of anomeric linkages and different branching patterns, potentially giving rise to many isomers. This level of complexity is one of the main reasons that identification of exact glycan structures in biological samples still lags behind that of other biomolecules. Here, we introduce a methodology to identify isomeric N‐glycans by determining gas phase conformer distributions (CDs) by measuring arrival time distributions (ATDs) using drift‐tube ion mobility spectrometry‐mass spectrometry. Key to the approach is the use of a range of well‐defined synthetic glycans that made it possible to investigate conformer distributions in the gas phase of isomeric glycans in a systematic manner. In addition, we have computed CD fingerprints by molecular dynamics (MD) simulation, which compared well with experimentally determined CDs. It supports that ATDs resemble conformational populations in the gas phase and offer the prospect that such an approach can contribute to generating a library of CCS distributions (CCSDs) for structure identification. Well‐defined synthetic glycans were used to show that ATDs in IMS‐MS resemble gas‐phase conformational populations, which was also confirmed by molecular dynamics simulation. By applying a database with intrinsic gas‐phase conformer distribution fingerprints, protein‐released N‐glycans, including isomeric structures, could be identified rapidly and unambiguously without the need for MS/MS experiments. |
| Databáze: | OpenAIRE |
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