A Peptide Molecule Mimicking the Copper(II) Transport Site of Human Serum Albumin

Catalytic metallodrugs targeting HCV IRES RNA

“…Moreover, the ligand stabilizes the Cu 3+/2+ redox states and does not permit formation of the labile Cu + state, while other physiological transition metals appear to have a lower affinity for the ATCUN sequence, thereby reducing the likelihood of metal exchange in the body. NMR, EPR, visible spectroscopy and X-ray crystallography are consistent with divalent metal ion coordinated in a square planar configuration, [15][16][17][18] leaving two faces accessible for binding to a target molecule.…”

“…[7][8][9][10][11] The metallodrugs described herein incorporate an N-terminal ATCUN (amino-terminal copper and nickel) binding motif that is found naturally at the N-terminus of many albumins 12 as well as natural peptides such as histatin 5 13 and neuromedin. 14 ATCUN peptides bind copper and nickel with very high affinity (K D B 1.18 Â 10 À16 M), 15 a prerequisite for cellular use. Moreover, the ligand stabilizes the Cu 3+/2+ redox states and does not permit formation of the labile Cu + state, while other physiological transition metals appear to have a lower affinity for the ATCUN sequence, thereby reducing the likelihood of metal exchange in the body.…”

Superoxide generation catalyzed by the ozone-inducible plant peptides analogous to prion octarepeat motif

“…24 At least one His residue is required for anchoring Cu ion to each motif. 25,26 Human PrP has four distinct copper-binding motifs. Among such motifs, the octarepeat motif possessing 4-time-repeated amino acid octet (PHG GGW GQ), has been studied in details.…”

Inactivation of human angiotensin converting enzyme by copper peptide complexes containing ATCUN motifs

“…The concentrations of the Cu 2+ peptide complexes were determined spectrophotometrically, using e 528 nm y108 M 21 cm 21 for [GGH-Cu] 2 and y85 M 21 cm 21 for [KGHK-Cu] + , respectively. 23,24 Enzyme Assays: Recombinant human ACE activity was assayed (final volume of 100 mL) at 37 uC in a buffer consisting of 50 mM HEPES containing 300 mM NaCl and 10 mM ZnCl 2 (pH 7.4) with 10 mM internally quenched fluorogenic peptide substrate, Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(Dnp)-OH (R&D Systems Inc.) and 1 nM (13.1 ng) rhACE. Reactions were run in the wells of polystyrene 96-well microplates (PS white, Porvair).…”