Localization of Disulfide Bonds in Ribonuclease Using Low pH Trypsin and LC-ESI-QTOF-MS

We evaluated a method to localize disulfide bonds in bovine pancreatic ribonuclease (RNase) by applying low pH trypsin protein digestion with a bottom-up LC-ESI-QTOF-MS approach. The goal was to minimize disulfide bond scrambling during sample preparation. By using N-ethylmaleimide (NEM) for alkylat...

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Main Authors: Amélie Bornex, Saša M. Miladinović
Format: Article
Language:deu
Published: Swiss Chemical Society 2024-12-01
Series:CHIMIA
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Online Access:https://www.chimia.ch/chimia/article/view/7475
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author Amélie Bornex
Saša M. Miladinović
author_facet Amélie Bornex
Saša M. Miladinović
author_sort Amélie Bornex
collection DOAJ
description We evaluated a method to localize disulfide bonds in bovine pancreatic ribonuclease (RNase) by applying low pH trypsin protein digestion with a bottom-up LC-ESI-QTOF-MS approach. The goal was to minimize disulfide bond scrambling during sample preparation. By using N-ethylmaleimide (NEM) for alkylation of free cysteines, we achieved 92% sequence coverage and successfully identified the native disulfide bonds between specific cysteine residues. However, scrambled disulfide bonds were also observed. Our results indicate that while this low pH digestion method helps preserve native disulfide bonds, further refinement is needed to fully prevent disulfide bond rearrangement during sample preparation.
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spelling doaj-art-e072ba65d2df4a938d18aa4dcd3919292025-08-20T02:29:51ZdeuSwiss Chemical SocietyCHIMIA0009-42932673-24242024-12-01781210.2533/chimia.2024.881Localization of Disulfide Bonds in Ribonuclease Using Low pH Trypsin and LC-ESI-QTOF-MSAmélie Bornex0Saša M. Miladinović1HES-SO Valais-Wallis, University of Applied Sciences, Institute of Life Sciences, CH-1950 Sion; Lonza AG, CH-3930 VispHES-SO Valais-Wallis, University of Applied Sciences, Institute of Life Sciences, CH-1950 SionWe evaluated a method to localize disulfide bonds in bovine pancreatic ribonuclease (RNase) by applying low pH trypsin protein digestion with a bottom-up LC-ESI-QTOF-MS approach. The goal was to minimize disulfide bond scrambling during sample preparation. By using N-ethylmaleimide (NEM) for alkylation of free cysteines, we achieved 92% sequence coverage and successfully identified the native disulfide bonds between specific cysteine residues. However, scrambled disulfide bonds were also observed. Our results indicate that while this low pH digestion method helps preserve native disulfide bonds, further refinement is needed to fully prevent disulfide bond rearrangement during sample preparation. https://www.chimia.ch/chimia/article/view/7475Bottom-up proteomicsDisulphide bondsLC-MSLow pH trypsin
spellingShingle Amélie Bornex
Saša M. Miladinović
Localization of Disulfide Bonds in Ribonuclease Using Low pH Trypsin and LC-ESI-QTOF-MS
CHIMIA
Bottom-up proteomics
Disulphide bonds
LC-MS
Low pH trypsin
title Localization of Disulfide Bonds in Ribonuclease Using Low pH Trypsin and LC-ESI-QTOF-MS
title_full Localization of Disulfide Bonds in Ribonuclease Using Low pH Trypsin and LC-ESI-QTOF-MS
title_fullStr Localization of Disulfide Bonds in Ribonuclease Using Low pH Trypsin and LC-ESI-QTOF-MS
title_full_unstemmed Localization of Disulfide Bonds in Ribonuclease Using Low pH Trypsin and LC-ESI-QTOF-MS
title_short Localization of Disulfide Bonds in Ribonuclease Using Low pH Trypsin and LC-ESI-QTOF-MS
title_sort localization of disulfide bonds in ribonuclease using low ph trypsin and lc esi qtof ms
topic Bottom-up proteomics
Disulphide bonds
LC-MS
Low pH trypsin
url https://www.chimia.ch/chimia/article/view/7475
work_keys_str_mv AT ameliebornex localizationofdisulfidebondsinribonucleaseusinglowphtrypsinandlcesiqtofms
AT sasammiladinovic localizationofdisulfidebondsinribonucleaseusinglowphtrypsinandlcesiqtofms