دورية أكاديمية
CHRISTMAS: Chiral Pair Isobaric Labeling Strategy for Multiplexed Absolute Quantitation of Enantiomeric Amino Acids
| العنوان: | CHRISTMAS: Chiral Pair Isobaric Labeling Strategy for Multiplexed Absolute Quantitation of Enantiomeric Amino Acids |
|---|---|
| المؤلفون: | Zhijun Zhu, Shuling Xu, Zicong Wang, Daniel G. Delafield, Michael J. Rigby, Gaoyuan Lu, Ting-Jia Gu, Peng-Kai Liu, Min Ma, Luigi Puglielli, Lingjun Li |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Biophysics, Biochemistry, Cell Biology, Genetics, Physiology, Pharmacology, Biotechnology, Immunology, Chemical Sciences not elsewhere classified, suitable internal standards, single step tagging, complex biological matrices, combined signal intensities, also significantly boosts, challenging enantiomeric separation, multiplexed absolute quantitation, enables absolute quantitation, st , r , quantitative strategy christmas, ch , , chromatographic separation, olute quantitation, n <, sobaric labeling, significant presence, resolved quantification, reagents offers, mouse brains |
| الوصف: | Amino acids (AAs) in the d-form are involved in multiple pivotal neurological processes, although their l-enantiomers are most commonly found. Mass spectrometry-based analysis of low-abundance d-AAs has been hindered by challenging enantiomeric separation from l-AAs, low sensitivity for detection, and lack of suitable internal standards for accurate quantification. To address these critical gaps, N,N -dimethyl-l-leucine (l-DiLeu) tags are first validated as novel chiral derivatization reagents for chromatographic separation of 20 pairs of d/l-AAs, allowing the construction of a 4-plex isobaric labeling strategy for enantiomer-resolved quantification through single step tagging. Additionally, the creative design of N,N -dimethyl-d-leucine (d-DiLeu) reagents offers an alternative approach to generate analytically equivalent internal references of d-AAs using d-DiLeu-labeled l-AAs. By labeling cost-effective l-AA standards using paired d- and l-DiLeu, this approach not only enables absolute quantitation of both d-AAs and l-AAs from complex biological matrices with enhanced precision but also significantly boosts the combined signal intensities from all isobaric channels, greatly improving the detection and quantitation of low-abundance AAs, particularly d-AAs. We term this quantitative strategy CHRISTMAS, which stands for ch iral pai r i sobaric labeling st rategy for m ultiplexed a b s olute quantitation. Leveraging the ion mobility collision cross section (CCS) alignment, interferences from coeluting isomers/isobars are effectively filtered out to provide improved quantitative accuracy. From wild-type and Alzheimer’s disease (AD) mouse brains, we successfully quantified 20 l-AAs and 5 d-AAs. The significant presence and differential trends of certain d-AAs compared to those of their l-counterparts provide valuable insights into the involvement of d-AAs in aging, AD progression, and neurodegeneration. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/journal_contribution/CHRISTMAS_Chiral_Pair_Isobaric_Labeling_Strategy_for_Multiplexed_Absolute_Quantitation_of_Enantiomeric_Amino_Acids/24700917Test |
| DOI: | 10.1021/acs.analchem.3c03847.s001 |
| الإتاحة: | https://doi.org/10.1021/acs.analchem.3c03847.s001Test https://figshare.com/articles/journal_contribution/CHRISTMAS_Chiral_Pair_Isobaric_Labeling_Strategy_for_Multiplexed_Absolute_Quantitation_of_Enantiomeric_Amino_Acids/24700917Test |
| حقوق: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.E9212A21 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.analchem.3c03847.s001 |
|---|