Influence of amino acid sequence in a peptidic Cu+-responsive luminescent probe inspired by the copper chaperone CusF.

Copper(i) is a soft metal ion that plays an essential role in living organisms and Cu+-responsive probes are required to detect Cu+ ions in physiological conditions and understand its homeostasis as well as the diseases associated with its misregulation. In this article, we describe a series of cyclic peptides, which are structurally related to the copper chaperone CusF, and that behave as Cu+-repsonsive probes. These peptide probes comprise the 16-amino acid loop of CusF cyclized by a ß-turn inducer dipeptide and functionalized by a Tb3+ complex for its luminescence properties. The mechanism of luminescence enhancement relies on the modulation of the antenna effect between a tryptophan residue and the Tb3+ ion within the probe when Cu+ forms a cation-π interaction with the tryptophan. Here, we investigate the influence of the amino acid sequence of these cyclic peptides on the copper-induced modulation of Tb3+ emission and show that the rigid ß-turn inducer Aib-d-Pro and insertion of the Tb3+ complex close to its tryptophan antenna are required to obtain turn-on Cu+ responsive probes. We also show that the amino acid sequence, especially the number and position of proline residues has a significant impact on metal-induced luminescence enhancement and metal-binding constant of the probes.

Model peptide studies of Ag+ binding sites from the silver resistance protein SilE.

Using model peptides, each of the nine MX2H or HXnM (n = 1, 2) motifs of the silver resistance protein SilE has been shown to coordinate to one Ag+ ion by its histidine and methionine residues with Kd in the µM range. This suggests an Ag+ buffering role for SilE in the case of high Ag+ overload.

Biomimetic copper(I)--CO complexes: a structural and dynamic study of a cali.

Four novel calix[6]arene-based cuprous complexes are described. They present a biomimetic tris(imidazole) coordination core associated with a hydrophobic cavity that wraps the apical binding site. Each differs from the other by the methyl or ethyl substituents present on the phenoxyl groups (OR1) and on the imidazole arms (NR2) of the calix[6]arene structure. In solution, stable CO complexes were obtained. We have investigated their geometrical and dynamic properties with respect to the steric demand. IR and NMR studies revealed that, in solution, these complexes adopted two distinct conformations. The preferred conformation was dictated only by the size of the OR1 group. When R1 was an ethyl group, the complex preferentially adopted a flattened C3-symmetrical structure. The corresponding helical enantiomers were in conformational equilibrium, which, however, was slow on the 1H NMR time scale at -80 degrees C. When R1 was a methyl group, the low-temperature NMR spectra revealed the partial inclusion of one tBu group. The complex wobbled between three dissymmetric but equivalent conformations. Hence, small differences in the steric demand of the calixarene's skeleton changed the geometry and dynamics of the system. Indeed, this supramolecular control was promoted by the strong conformational coupling between the metal center and the host structure. Interestingly, this was not only the result of a covalent preorganization, but also stemmed from weak interactions within the hydrophobic pocket. The vibrational spectra of the bound CO were revealed to be a sensitive gauge of this supramolecular behavior, similar to copper proteins in which allosteric effects are common.