title: Modular and tunable chemosensor scaffold for divalent zinc.
abstract: A modular peptide scaffold has been developed for fluorescent sensing of divalent zinc. The signaling component of the chemosensor is the chelation-sensitive fluorophore 8-hydroxy-5-(N,N-dimethylsulfonamido)-2-methylquinoline, which is prepared as the protected amino acid derivative Fmoc-Sox-OH and integrated into peptide sequences. Nineteen synthetic peptides incorporating the signaling element exhibit a range of affinities for Zn(2+) through variation of the type and number of Zn(2+) ligands, ligand arrangement and the beta-turn sequence that acts as a preorganization element between the ligands. The stoichiometry of the peptide-Zn(2+) complexes is evaluated by several criteria. The fluorescence response of these peptides to pH and various important metal ions is reported. Eleven of these sequences form only 1:1 complexes with Zn(2+) and their affinities range from 10 nM to nearly 1 microM. When used in concert, these sensors can provide Zn(2+) concentration information in a valuable range.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Shults
authors.forename: Dierdre A
authors.initials: DA
authors.lastname: Pearce
authors.forename: Barbara
authors.initials: B
authors.lastname: Imperiali
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D015374:Biosensing Techniques / Q000379:methods*; D002413:Cations, Divalent; D005449:Fluorenes / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013449:Sulfonamides / Q000737:chemistry; D015032:Zinc / Q000032:analysis*
chemical_list: D000596:Amino Acids; D002413:Cations, Divalent; D005449:Fluorenes; D005456:Fluorescent Dyes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009842:Oligopeptides; D011804:Quinolines; D013449:Sulfonamides; D015032:Zinc