Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity.

ABSTRACT: We demonstrate phage-display screening on self-assembled ligands that enables the identification of oligopeptides that selectively bind dynamic supramolecular targets over their unassembled counterparts. The concept is demonstrated through panning of a phage-display oligopeptide library against supramolecular tyrosine-phosphate ligands using 9-fluorenylmethoxycarbonyl-phenylalanine-tyrosine-phosphate (Fmoc-FpY) micellar aggregates as targets. The 14 selected peptides showed no sequence consensus but were enriched in cationic and proline residues. The lead peptide, KVYFSIPWRVPM-NH₂ (P7) was found to bind to the Fmoc-FpY ligand exclusively in its self-assembled state with K _D = 74 ± 3 μM. Circular dichroism, NMR and molecular dynamics simulations re

SUBMITTER: Pina AS 

PROVIDER: S-EPMC8694286 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature