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Acid‐based approach for separation of peptide epimers using IM‐MS
Author(s) -
Zimnicka Magdalena M.,
Troć Anna
Publication year - 2019
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.4362
Subject(s) - chemistry , epimer , peptide , ion mobility spectrometry , protonation , tripeptide , carboxylate , amide , sulfonic acid , dissociation (chemistry) , amino acid , stereochemistry , ion , mass spectrometry , chromatography , organic chemistry , biochemistry
Chiral molecules frequently remain undistinguishable using ion mobility mass spectrometry (IM‐MS), due to insufficient differences of their collision cross sections at the available mobility resolution of the ion mobility drift tubes. The influence of the complexation with organic acids on the ion mobility separation of peptide epimers is evaluated using traveling‐wave ion mobility (TWIMS). The examined epimeric tripeptides containing Arg residue with the sequence: Ac‐Phe‐Arg‐Trp‐NH 2 formed stable complexes in the gas phase, and under the increased pressure in ion mobility drift tube, noncovalent associates formed with carboxylic or sulfonic monoacids and diacids with chiral variation of certain acids. Overall, the complexation with an acid leads to the improvement in stereodifferentiation among epimeric peptides, in comparison to the analysis of pure epimers. Detailed characterization of peptide epimer‐acid associates obtained for dibenzoyl‐D‐tartaric acid by theoretical calculations and collisional dissociation studies revealed that the presence of multiple hydrogen bonding interactions between carboxylate anions and hydrogens from N―H of both the guanidinium group of arginine and the indole of tryptophan, as well as the amide backbone hydrogens in the peptide, is responsible for stability of acid‐peptide complexes and for their differentiation in the ion mobility drift tube. The specificity of complex formation toward Arg was determined in terms of complex stability. Based on the reported results, we present general conclusions regarding the utility of the acid‐based complexation in the separation of peptide isomers.