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Detection and analysis of chiral molecules as disease biomarkers - PubMed

Review

Detection and analysis of chiral molecules as disease biomarkers

Yaoran Liu et al. Nat Rev Chem. 2023 May.

Abstract

The chirality of small metabolic molecules is important in controlling physiological processes and indicating the health status of humans. Abnormal enantiomeric ratios of chiral molecules in biofluids and tissues occur in many diseases, including cancers and kidney and brain diseases. Thus, chiral small molecules are promising biomarkers for disease diagnosis, prognosis, adverse drug-effect monitoring, pharmacodynamic studies and personalized medicine. However, it remains difficult to achieve cost-effective and reliable analysis of small chiral molecules in clinical procedures, in part owing to their large variety and low concentration. In this Review, we describe current and emerging techniques that detect and quantify small-molecule enantiomers and their biological importance.

© 2023. Springer Nature Limited.

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Conflict of interest statement

Competing interests

The authors declare no competing interests.

Figures

Fig. 1 |
Fig. 1 |. Influential factors for ‘abnormal’ chirality, common chiral biomarkers and associated diseases.

Internal and external factors can induce abnormal concentrations of chiral biomarkers in the human body, which are associated with various diseases.

Fig. 2 |
Fig. 2 |. Sample preparation before chiral detection.

Filtration and extraction of chiral small molecules from biofluids and tissues.

Fig. 3 |
Fig. 3 |. Chiral detection of small molecules via chromatography and capillary electrophoresis coupled to mass spectrometry.

After sample preparation, small molecules can be enantiomerically separated using a chiral selector, such as a chiral derivatization reagent (CDR), a chiral mobile phase or a chiral stationary phase during chromatography. The small molecules can also be enantioselectively separated using chiral capillary electrophoresis. The enantiomers, which have different retention times, are separated and resolved by mass spectrometry.

Fig. 4 |
Fig. 4 |. Chiral detection of small molecules with NMR spectroscopy and an enzymatic assay.

a, After sample preparation, small molecules, with the addition of chiral derivatization reagents (CDRs), can be enantiomerically resolved using nuclear magnetic resonance (NMR) spectroscopy. The intensity between

d

and

l

peaks on the NMR spectrum reflects the enantiomeric excess. b, After sample preparation, enzymatic probes with enantiomeric selectivity are added to samples to form conjugated molecules. Fluorescent imaging of a colorimetric assay is used to determine the concentration of the targeted enantiomers. H0, magnetic field.

Fig. 5 |
Fig. 5 |. Chiral detection using chiroptical spectroscopy.

Several chiroptical methods and surface-enhanced strategies can be used to detect the chirality and stereochemical purity of small molecules. λ, wavelength; CD, circular dichroism; f, frequency; ROA, Raman optical activity; VCD, vibrational circular dichroism.

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References

    1. Etzioni R et al. The case for early detection. Nat. Rev. Cancer 3, 243–252 (2003). - PubMed
    1. Hanash SM, Pitteri SJ & Faca VM Mining the plasma proteome for cancer biomarkers. Nature 452, 571–579 (2008). - PubMed
    1. Blennow K, Hampel H, Weiner M & Zetterberg H Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat. Rev. Neurol 6, 131–144 (2010). - PubMed
    1. Rinschen MM, Ivanisevic J, Giera M & Siuzdak G Identification of bioactive metabolites using activity metabolomics. Nat. Rev. Mol. Cell Biol 20, 353–367 (2019). - PMC - PubMed
    1. Rochfort S Metabolomics reviewed: a new “omics” platform technology for systems biology and implications for natural products research. J. Nat. Prod 68, 1813–1820 (2005). - PubMed

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