Affinity Selection from Synthetic Peptide Libraries Enabled by De Novo MS/MS Sequencing

Abstract Recently, de novo MS/MS peptide sequencing has enabled the application of affinity selections to synthetic mixtures that approach diversity phage libraries (> 10 8 random peptides). In conjunction with ‘split-mix’ solid phase synthesis access equimolar mixtures, this provides a straightforward means examine considerably higher than been feasible historically. Here, we offer critical perspective on work, report emerging data, and highlight opportunities for further methods refinement. With continued development, ‘affinity selection–mass spectrometry’ may become complimentary display, in vitro selection, DNA-encoded discovery ligands modulate protein function.