Selenopeptide Phage Display: Chemical Modification and Applications
Lana Saleh
New England Biolabs, 240 County Rd, Ipswich, MA 01938
Abstract:
Chemical modification of the surface of bacteriophage can expand the limited chemical diversity of the canonical amino acids in the phage coat. Incorporation of selenocysteine into the coat protein pIII can confer vastly improved selectivity in chemical modification of the phage. We report the use of selenocysteine-directed chemical modification to construct a phage imaging system tailored toward in vivo localization of adenosine receptors (ARs). An AR ligand covalently tethered to selenonopeptide displayed on pIII of a fluorescently labeled M13 phage directs delivery of the phage probe to recombinant ARs expressed on HEK cells. We demonstrate (1) efficiency and selectivity in conjugating AR ligands to seleno-pIII, (2) differential binding of modified and unmodified phage to membrane ARs, and (3) enhanced receptor-specific avidity through pentavalent interactions by the pIII-ligand conjugates. We will also discuss the use of phage-displayed selenopeptides for chimeric library screening and catalysis-based screening for novel enzyme activities.
