New insights for pursuing high relaxivity MRI agents from modelling the binding interaction of Gd(III) chelates to HSA.
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Chelating Agents↗
Biomedical subjects
Dario Longo
Publications and source records attributed to Dario Longo.
Magnetic resonance imaging visualization of targeted cells by the internalization of supramolecular adducts formed between avidin and biotinylated Gd3+ chelates.
The high binding affinity between avidin and biotin has been exploited to develop a procedure for magnetic resonance imaging (MRI) visualization of target cells. SHIN3 and PANC1 tumor cell lines have been used as target cells because they possess on their membranes galactosyl receptors able to bind avidin molecules. Avidin-Gd chelate adducts have been built by using two Gd complexes containing one (Gd-I) and two (Gd-II) biotin residues, respectively. The relaxivities of such supramolecular adducts are significantly higher than those shown by free Gd-I and Gd-II. There is evidence of the occurrence of multilayered adducts in which the bis-biotinylated Gd(3+) complex acts as a bridge between adjacent avidin molecules. MRI differentiation of labeled versus unlabeled cells has been attained when approximately 6 x 10(8) Gd units were internalized in each cell. Furthermore, there is a marked decrease in the measured intracellular T(1) relaxivity as the number of internalized Gd complexes increases, probably owing to too short relaxation times of endosomic water protons with respect to their diffusion lifetime.
Avidin↗
Docking studies on NSAID/COX-2 isozyme complexes using contact statistics analysis.
The selective inhibition of COX-2 isozymes should lead to a new generation of NSAIDs with significantly reduced side effects; e.g. celecoxib (Celebrex) and rofecoxib (Vioxx). To obtain inhibitors with higher selectivity it has become essential to gain additional insight into the details of the interactions between COX isozymes-and NSAIDs. Although X-ray structures of COX-2 complexed with a small number of ligands are available, experimental data are missing for two well-known selective COX-2 inhibitors (rofecoxib and nimesulide) and docking results reported are controversial. We use a combination of a traditional docking procedure with a new computational tool (Contact Statistics analysis) that identifies the best orientation among a number of solutions to shed some light on this topic.
Algorithms↗