Highly efficient grafting of hetero-complementary amidinium and carboxylate hydrogen-bonding/ionic pairs onto polymer surfaces

We describe a grafting methodology, based on thiol-fluoroarene chemistry, to efficiently incorporate complementary hydrogen-bonding carboxylate and amidinium groups into polymer backbones. The process was optimized both in solution and on the surface of processed films, with the aim to produce materials showing hetero-complementary adhesionPDC2021-121487-I00, ERC-PoC-75479

Electrochemical detection of glutathione S-transferase: An important enzyme in the cell protective mechanism against oxidative stress

Oxidative stress arises when the antioxidant capacity of cells to clean the excess production of reactive oxygen species (ROS) decreases. Several human diseases seem to be related with an increment in the oxidative stress. In this regard, GSH present in the cells works by neutralizing ROS and other xenobiotics through the glutathione S-transferase (GST) enzyme. Thus, the level of expression of GST is an important factor in determining the sensitivity of cells to toxic chemicals or xenobiotic compounds. Therefore, the detection of GST levels is fundamental in the clinical diagnosis of ROS-related diseases. Here, we describe a methodology, based on the voltammetric properties of the ferrocene group (used as electrochemical probe), which can be applied for selective detection of GST levels in human cells. The electrochemical signal measured is associated to the specific interaction of a ferrocenyl-GSH derivate with the G- and H-sites of this enzyme

Binding ability properties of β-cyclodextrin dimers linked through their secondary faces towards cancer chemotherapeutic agent methotrexate

The binding ability properties of two β-cyclodextrin dimers linked through their secondary faces by short, rigid spacer arms towards the cancer chemotherapeutic agent methotrexate were studied by ITC and NMR (1D and ROESY) experiments. Both dimers are able to bind two molecules of methotrexate with a binding constant between 2.4 and 3.5 times higher than that for native β-cyclodextrin, the dimer having the shortest linker forming the most stable complex

β‑Cyclodextrin-Bearing Gold Glyconanoparticles for the Development of Site Specific Drug Delivery Systems

Three novel gold nanoparticles containing multiple long, flexible linkers decorated with lactose, β-cyclodextrin and both simultaneously have been prepared. The interaction of such nanoparticles with β-D-galactose-recognizing lectins peanut agglutinin (PNA) and human galectin-3 (Gal-3) was demonstrated by UV-Vis studies. Gal-3 is well-known to be overexpressed in several human tumors and can act as biorecognizable target. This technique also allowed us to estimate their loading capability toward the anticancer drug methotrexate (MTX). Both results make these glyconanoparticles potential site-specific delivery systems for anticancer drugs

Binding properties of ferrocene–glutathione conjugates as inhibitors and sensors for glutathione S-transferases

The binding properties of two electroactive glutathione–ferrocene conjugates that consist in glutathione attached to one or both of the cyclopentadienyl rings of ferrocene (GSFc and GSFcSG), to Schistosoma japonica glutathione S-transferase (SjGST) were studied by spectroscopy fluorescence, isothermal titration calorimetry (ITC) and differential pulse voltammetry (DPV). Such ferrocene conjugates resulted to be competitive inhibitors of glutathione S-transferase with an increased binding affinity relative to the natural substrate glutathione (GSH). We found that the conjugate having two glutathione units (GSFcSG) exhibits an affinity for SjGST approximately two orders of magnitude higher than GSH. Furthermore, it shows negative cooperativity with the affinity for the second binding site two orders of magnitude lower than that for the first one. We propose that the reason for such negative cooperativity is steric since, i) the obtained thermodynamic parameters do not indicate profound conformational changes upon GSFcSG binding and ii) docking studies have shown that, when bound, part of the first bound ligand invades the second site due to its large size. In addition, voltammetric measurements show a strong decrease of the peak current upon binding of ferrocene–glutathione conjugates to SjGST and provide very similar K values than those obtained by ITC. Moreover, the sensing ability, expressed by the sensitivity parameter shows that GSFcSG is much more sensitive than GSFc, for the detection of SjGST

Poly(amido amine)-Based Mannose-Glycodendrimers As Multielectron Redox Probes for Improving Lectin Sensing

An easy-to-prepare series of electroactive PAMAM-based dendrimers of generations G0 to G2 having mannopyranosylferrocenyl moieties in the periphery to detect carbohydrate-protein interactions is reported. The synthesis involved the functionalization of the PAMAM surface with azidomethylferrocenyl groups and subsequent coupling of mannoside units by Cu(I)-catalyzed Huisgen reaction. The binding affinity of the series of electroactive glycodendrimers was studied by isothermal titration calorimetry (ITC) and differential pulse voltammetry (DPV). Upon complexation of the glycodendrimers conjugates with prototypical concanavalin A (Con A), voltammograms showed a decrease of the peak current. Such dendrimers showed a notable improvement of redox sensing abilities towards Con A when compared with mono- and divalent analogues, based on both the glycoside multivalent and ferrocene dendritic effects