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Surface-enhanced Raman spectroscopy for drug discovery: peptide-RNA binding

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Abstract

The ever-growing demand for new drugs highlights the need to develop novel cost- and time-effective techniques for drug discovery. Surface-enhanced Raman spectroscopy (SERS) is an emerging ultrasensitive and label-free technique that allows for the efficient detection and characterization of molecular interactions. We have recently developed a SERS platform for detecting a single protein molecule linked to a gold substrate (Almehmadi et al. Scientific Reports 2019). In this study, we extended the approach to probe the binding of potential drugs to RNA targets. To demonstrate the proof of concept, two 16-amino acid residue peptides with close primary structures and different binding affinities to the RNA CUG repeat related to myotonic dystrophy were tested. Three-microliter solutions of the RNA repeat with these peptides at nanomolar concentrations were probed using the developed approach, and the binding of only one peptide was demonstrated. The SER spectra exhibited significant fluctuations along with a sudden strong enhancement as spectra were collected consecutively from individual spots. Principal component analysis (PCA) of the SER spectral datasets indicated that free RNA repeats could be differentiated from those complexed with a peptide with 100% accuracy. The developed SERS platform provides a novel opportunity for label-free screening of RNA-binding peptides for drug discovery.

Graphical abstract

Schematic representation of the SERS platform for drug discovery developed in this study

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Fig. 1
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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the National Science Foundation (CHE-1845486, J.S.) and National Institutes of Health (NIH, R35GM124720, K.H., and R35GM138336, Q.Z.) for the financial support. We would like to thank Dr. David S. Burz for providing technical help with the electroplating setup, Dr. Natalya Tokranova for her help with the SERS substrate preparation, and Dr. Peter de B. Harrington for his insights regarding the PCA.

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Authors and Affiliations

  1. Department of Chemistry, University at Albany, SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA

    Lamyaa M. Almehmadi, Vibhav A. Valsangkar, Qiang Zhang, Jia Sheng & Igor K. Lednev

  2. College of Arts and Science, RNA Institute, University at Albany, SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA

    Lamyaa M. Almehmadi, Vibhav A. Valsangkar, Ken Halvorsen, Jia Sheng & Igor K. Lednev

Authors
  1. Lamyaa M. Almehmadi
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  2. Vibhav A. Valsangkar
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  3. Ken Halvorsen
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  4. Qiang Zhang
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  5. Jia Sheng
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  6. Igor K. Lednev
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Contributions

I.K.L. and J.S. conceived the project. L.M.A. conducted the experiments, including sample preparation, SERS substrate manufacturing, and SERS spectroscopic data acquisition. V.V. and K.H. conducted the ITC and gel shifting experiments. L.M.A. and I.K.L. analyzed the SERS data. Q.Z. synthesized the initial peptide pool. L.M.A. and I.K.L. wrote the manuscript with input from all authors. All of the authors have approved the final version of the manuscript.

Corresponding authors

Correspondence to Jia Sheng or Igor K. Lednev.

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Almehmadi, L.M., Valsangkar, V.A., Halvorsen, K. et al. Surface-enhanced Raman spectroscopy for drug discovery: peptide-RNA binding. Anal Bioanal Chem 414, 6009–6016 (2022). https://doi.org/10.1007/s00216-022-04190-5

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  • DOI: https://doi.org/10.1007/s00216-022-04190-5

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