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  • Review Article
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Detection and analysis of chiral molecules as disease biomarkers

Nature Reviews Chemistry volume 7, pages 355–373 (2023)Cite this article

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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.

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Fig. 1: Influential factors for ‘abnormal’ chirality, common chiral biomarkers and associated diseases.
Fig. 2: Sample preparation before chiral detection.
Fig. 3: Chiral detection of small molecules via chromatography and capillary electrophoresis coupled to mass spectrometry.
Fig. 4: Chiral detection of small molecules with NMR spectroscopy and an enzymatic assay.
Fig. 5: Chiral detection using chiroptical spectroscopy.

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Acknowledgements

Y.L., Z.W. and Y.Z. acknowledge the financial support of the National Institute of General Medical Sciences of the National Institutes of Health (NIH) (R01GM146962) and National Science Foundation (NSF) (ECCS-2001650). D.W.A acknowledges the support of the R. A. Welch Foundation (Y-0026). H.W. acknowledges the financial support of Israel Science Foundation 337/19, Ministry of Health, and Allen and Jewell Prince Center for Neurodegenerative Disorders of the Brain.

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Authors and Affiliations

  1. Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, TX, USA

    Yaoran Liu & Yuebing Zheng

  2. Walker Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX, USA

    Zilong Wu & Yuebing Zheng

  3. Texas Materials Institute, The University of Texas at Austin, Austin, TX, USA

    Zilong Wu & Yuebing Zheng

  4. Department of Chemistry & Biochemistry, University of Texas at Arlington, Arlington, TX, USA

    Daniel W. Armstrong

  5. Department of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    Herman Wolosker

  6. Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA

    Yuebing Zheng

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All authors collected data, wrote and edited the manuscript. Y.L. drafted the manuscript. D.W.A and H.W. provided substantial content. Y. L., Z. W. and Y. Z. conceived the content, and edited and finalized the manuscript.

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Correspondence to Zilong Wu, Daniel W. Armstrong, Herman Wolosker or Yuebing Zheng.

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Glossary

Chiral

The geometric property of a molecule that precludes it from being superimposable on its mirror image.

Chiral selectors

Chiral components in the chiral separation system that interact enantioselectively with the target chiral molecule.

Chiroptical

The optical properties related to the interaction of chirality.

Enantiomeric excess

The excess of one enantiomer over the other in a mixture of enantiomers.

Enantiomers

A pair of compounds that are not superposable onto their own mirror image.

Metabolites

Substances produced after metabolism (food, drugs or chemical digestion).

Metabolomics

A systematic study of chemical processes involving metabolites, the small-molecule substrates, intermediates and products of cell metabolism.

Metamaterials

Materials engineered to have a property that is not found in the equivalent naturally occurring materials.

Metasurfaces

2D thin film materials that can modulate the propagation of electromagnetic waves.

Multiplexed

A way of measuring the concentration of multiple biomarkers.

Recovery rates

The percentages of molecular concentration that can be recovered from the total concentration after physical or chemical processes.

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Liu, Y., Wu, Z., Armstrong, D.W. et al. Detection and analysis of chiral molecules as disease biomarkers. Nat Rev Chem 7, 355–373 (2023). https://doi.org/10.1038/s41570-023-00476-z

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