title: Identification of metal ion binding peptides containing unnatural amino acids by phage display.
abstract: The bidentate metal binding amino acid bipyridylalanine (BpyAla) was incorporated into a disulfide linked cyclic peptide phage displayed library to identify metal ion binding peptides. Selection against Ni(2+)-nitrilotriacetic acid (NTA) enriched for sequences containing histidine and BpyAla. BpyAla predominated when selections were carried out at lower pH, consistent with the differential pKa's of histidine and BpyAla. Two peptides containing BpyAla were synthesized and found to bind Ni(2+) with low micromolar dissociation constants. Incorporation of BpyAla and other metal binding amino acids into peptide and protein libraries should enable the evolution of novel binding and catalytic activities.
authors.affiliation: Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Day
authors.forename: Chan Hyuk
authors.initials: CH
authors.lastname: Kim
authors.forename: Vaughn V
authors.initials: VV
authors.lastname: Smider
authors.forename: Peter G
authors.initials: PG
authors.lastname: Schultz
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D007700:Kinetics; D008670:Metals / Q000737:chemistry / Q000378:metabolism*; D009532:Nickel / Q000737:chemistry / Q000378:metabolism; D009571:Nitrilotriacetic Acid / Q000737:chemistry; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D000596:Amino Acids; D007477:Ions; D008670:Metals; D019151:Peptide Library; D010456:Peptides, Cyclic; D015082:2,2'-Dipyridyl; D009532:Nickel; D009571:Nitrilotriacetic Acid