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Leveraging nature’s biomolecular designs in next-generation protein sequencing reagent development



Jennifer A. Tullman, John P. Marino, Zvi Kelman


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.
Applied Microbiology and Biotechnology


Aptamer, affinity reagents, fluoro-sequencing, NAAB, N-terminal amino acid binder, protein sequencing


Tullman, J. , Marino, J. and Kelman, Z. (2020), Leveraging nature’s biomolecular designs in next-generation protein sequencing reagent development, Applied Microbiology and Biotechnology, [online], (Accessed April 18, 2024)
Created August 31, 2020, Updated October 8, 2020