ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Bacterial Proteins/metabolism , Carrier Proteins/metabolism , Peptide Fragments/metabolism , Silver/metabolism , Bacterial Proteins/chemistry , Binding Sites , Carrier Proteins/chemistry , Drug Resistance, Bacterial/physiology , Glutamic Acid/chemistry , Glutamic Acid/metabolism , Histidine/chemistry , Histidine/metabolism , Methionine/chemistry , Methionine/metabolism , Peptide Fragments/chemical synthesis , Peptide Fragments/chemistry , Protein Binding , Silver/chemistryABSTRACT
Epidemiologic data strongly suggest that upper distribution of body fat and high plasminogen activator inhibitor (PAI) activity are risk factors for cardiovascular disease. Therefore, a link between these two parameters was evaluated by studying 51 menstrually active nondiabetic obese women. In this group positive correlations were observed between body mass index (BMI), waist to hip circumference ratio (W/H ratio, which estimates body fat distribution), plasma insulin, and PAI activity. In addition, plasma triglycerides were related to the W/H ratio and insulin and PAI activity. Partial correlations revealed that BMI was independently and solely related to W/H ratio, which was also independently related to plasma insulin, which in turn related to PAI activity. These results suggest that upper body fat distribution acts as a risk factor of cardiovascular disease through its association with high PAI activity.
