Abstract
Next-generation approaches for protein sequencing are now emerging that could have the potential to revolutionize the field in proteomics. One such sequencing method involves fluorescence-based imaging of immobilized peptides in which the N-terminal amino acid of a polypeptide is readout sequentially by a series of fluorescently labeled biomolecules. When selectively bound to a specific N-terminal amino acid, the NAAB (N-terminal amino acid binder) affinity reagent identifies the amino acid through its associated fluorescence tag. A key technical challenge in implementing this fluoro-sequencing approach is the need to develop NAAB affinity reagents with the high affinity and selectivity for specific N-terminal amino acids required for this biotechnology application. One approach to develop such a NAAB affinity reagent is to leverage naturally occurring biomolecules that bind amino acids and/or peptides. Here, we describe several candidate biomolecules that could be considered for this purpose and discuss the potential for developability of each.
Key points • Next-generation sequencing methods are emerging that could revolutionize proteomics. • Sequential readout of N-terminal amino acids by fluorescent-tagged affinity reagents. • Native peptide/amino acid binders can be engineered into affinity reagents. • Protein size and structure contribute to feasibility of reagent developability. |
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This work was supported by a National Institute of Standards and Technology (NIST) Innovation in Measurement Science Award.
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Tullman, J., Marino, J.P. & Kelman, Z. Leveraging nature’s biomolecular designs in next-generation protein sequencing reagent development. Appl Microbiol Biotechnol 104, 7261–7271 (2020). https://doi.org/10.1007/s00253-020-10745-2
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DOI: https://doi.org/10.1007/s00253-020-10745-2