Search results for "Models"
showing 10 items of 8211 documents
Photodynamics in stable complexes composed of a zinc porphyrin tripod and pyridyl porphyrins assembled by multiple coordination bonds
2010
A tripod zinc porphyrin (TPZn(3)) forms a stable 1:1 complex with gold(III) tetra(4-pyridyl)porphyrin (AuTPyP(+)) and free-base tris(4-pyridyl)porphyrin (2H-Py(3)P) in nonpolar solvents. The strong binding of TPZn(3) with AuTPyP(+) or 2H-Py(3)P results from the encapsulation of AuTPyP(+) or 2H-Py(3)P inside the cavity of TPZn(3) through multiple coordination bonds, as indicated by UV-vis-NIR, ESI-MS, (1)H NMR, electrochemistry and computational studies. The binding constants of monomer zinc porphyrin (MPZn) with AuTPyP(+) and 2H-Py(3)P drastically decrease as compared with TPZn(3). Detailed photophysical studies have been carried out on these composites using laser flash photolysis as well …
Biomimetic oxygen reduction by cofacial porphyrins at a liquid-liquid interface.
2012
Oxygen reduction catalyzed by cofacial metalloporphyrins at the 1,2-dichlorobenzene−water interface was studied with two lipophilic electron donors of similar driving force, 1,1'-dimethylferrocene (DMFc) and tetrathiafulvalene (TTF). The reaction produces mainly water and some hydrogen peroxide, but the mediator has a significant effect on the selectivity, as DMFc and the porphyrins themselves catalyze the decomposition and the further reduction of hydrogen peroxide. Density functional theory calculations indicate that the biscobaltporphyr- in, 4,5-bis(5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl))-9,9-dimethylxanthene, Co2(DPX), actually catalyzes oxygen reduction to hydrogen p…
Identifying three-way DNA junction-specific small-molecules
2012
Three-way junction DNA (TWJ-DNA, also known as 3WJ-DNA) is an alternative secondary DNA structure comprised of three duplex-DNAs that converge towards a single point, termed the branch point. This point is characterized by unique geometrical properties that make its specific targeting by synthetic small-molecules possible. Such a targeting has already been demonstrated in the solid state but not thoroughly biophysically investigated in solution. Herein, a set of simple biophysical assays has been developed to identify TWJ-specific small-molecule ligands; these assays, inspired by the considerable body of work that has been reported to characterize the interactions between small-molecules an…
Unusual Formation of a Stable 2D Copper Porphyrin Network
2013
Copper(II) 5,15-bis(diethoxyphosphoryl)-10,20-diphenylporphyrin was obtained and characterized by means of cyclic voltammetry, electron paramagnetic resonance, Fourier transform infrared, and UV-visible spectroscopy. Three crystalline forms were grown and studied by means of X-ray diffraction methods (single crystal and powder). The highly electron-withdrawing effect of phosphoryl groups attached directly to the porphyrin macrocycle results in a self-assembling process, with formation of a stable 2D coordination network, which is unusual for copper(II) porphyrins. The resulting 2D structure is a rare example of an assembly based on copper(II) porphyrins where the copper(II) central metal io…
In-silico screening of new potential Bcl-2/Bcl-xl inhibitors as apoptosis modulators
2008
One of the major problems in the fight against cancer is drug-resistance, which, at a molecular level, can be acquired through mutations able to deactivate apoptosis. In particular, proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-xl and Bcl-2, are overexpressed in many tumours. The development of new inhibitors of these proteins as potential anticancer therapeutics represents a new frontier. In this work, we carried out an in-silico screening of compounds from a free database of more than 2 million structures (ZINC database), which allowed us to identify 17 sulfonamide derivatives as new potential inhibitors; thes…
A Ser residue influences the structure and stability of a Pro-kinked transmembrane helix dimer
2012
AbstractWhen localized adjacent to a Pro-kink, Thr and Ser residues can form hydrogen bonds between their polar hydroxyl group and a backbone carbonyl oxygen and thereby modulate the actual bending angle of a distorted transmembrane α-helix. We have used the homo-dimeric transmembrane cytochrome b559′ to analyze the potential role of a highly conserved Ser residue for assembly and stabilization of transmembrane proteins. Mutation of the conserved Ser residue to Ala resulted in altered heme binding properties and in increased stability of the holo-protein, most likely by tolerating subtle structural rearrangements upon heme binding. The results suggest a crucial impact of an intrahelical Ser…
News from an Ancient World: Two Novel Astacin Metalloproteases from the Horseshoe Crab
2008
In this work, we report the cloning, heterologous expression, and characterization of two novel astacin proteases from the chelicerate Limulus polyphemus (horseshoe crab), designated as LAST (Limulus astacin) and LAST_MAM (Limulus astacin containing a MAM domain), respectively. The expression pattern showed ubiquitous occurrence of LAST_MAM, while LAST was predominantly restricted to the eyes and brain, indicating a function in the nervous system. Both enzymes contain the characteristic metzincin-type zinc-binding region and Met turn. While LAST is made up only of the typical prodomain and astacin-like protease domain, LAST_MAM contains an additional MAM (meprin A5 protein tyrosine phosphat…
Sizzled Is Unique among Secreted Frizzled-related Proteins for Its Ability to Specifically Inhibit Bone Morphogenetic Protein-1 (BMP-1)/Tolloid-like …
2012
BMP-1/tolloid-like proteinases (BTPs) are major enzymes involved in extracellular matrix assembly and activation of bioactive molecules, both growth factors and anti-angiogenic molecules. Although the control of BTP activity by several enhancing molecules is well established, the possibility that regulation also occurs through endogenous inhibitors is still debated. Secreted frizzled-related proteins (sFRPs) have been studied as possible candidates, with highly contradictory results, after the demonstration that sizzled, a sFRP found in Xenopus and zebrafish, was a potent inhibitor of Xenopus and zebrafish tolloid-like proteases. In this study, we demonstrate that mammalian sFRP-1, -2, and …
Tuning and Predicting Biological Affinity: Aryl Nitriles as Cysteine Protease Inhibitors
2012
A series of aryl nitrile-based ligands were prepared to investigate the effect of their electrophilicity on the affinity against the cysteine proteases rhodesain and human cathepsin L. Density functional theory calculations provided relative reactivities of the nitriles, enabling prediction of their biological affinity and cytotoxicity and a clear structure-activity relationship.
Flavonoids as noncompetitive inhibitors of Dengue virus NS2B-NS3 protease: Inhibition kinetics and docking studies
2014
NS2B-NS3 is a serine protease of the Dengue virus considered a key target in the search for new antiviral drugs. In this study flavonoids were found to be inhibitors of NS2B-NS3 proteases of the Dengue virus serotypes 2 and 3 with IC50 values ranging from 15 to 44 μM. Agathisflavone (1) and myricetin (4) turned out to be noncompetitive inhibitors of dengue virus serotype 2 NS2B-NS3 protease with Ki values of 11 and 4.7 μM, respectively. Docking studies propose a binding mode of the flavonoids in a specific allosteric binding site of the enzyme. Analysis of biomolecular interactions of quercetin (5) with NT647-NHS-labeled Dengue virus serotype 3 NS2B-NS3 protease by microscale thermophoresis…