Inhibitors of the chaperone Hsp90 are potentially useful as chemotherapeutic agents in cancer. This paper describes an application of fragment screening to Hsp90 using a combination of NMR and high throughput X-ray crystallography. The screening identified an aminopyrimidine with affinity in the high micromolar range and subsequent structure-based design allowed its optimization into a low nano...

a liquid membrane containing diethylene glycol monobutyl ether (2) shows specificity for k ion in transport while diethylene glycol dibutyl ether (1) was selective for na over k . as an extractant, ligand 2 exhibited pronounced extraction selectivity for k over na in comparison with ligand 1

Proteasome-mediated proteolysis modulates the cellular concentration of estrogen receptor-alpha (ERalpha) and is induced by treatment of cells with 17beta-estradiol. Herein, we show that multiple receptor agonists, including 17alpha-estradiol and estriol as well as the antagonist ICI-182780, stimulate proteasome-dependent proteolysis of ERalpha in a process that requires ligand binding to the r...

Here, new N,N′-dipyridoxyl(4,4''-diaminodiphenylether) Schiff-base ligand has been synthesized and characterized by IR, 1H NMR and mass spectrometry. Also, geometry optimization and theoretical assignment of IR spectrum of the ligand have been computed by employing density functional theory (DFT) method. Two pyridine rings and benzene rings in the bridge region are not in the same plane. The ca...

Understanding how to controllably modulate the efficiency of energy transfer in Förster resonance energy transfer (FRET)-based assemblies is critical to their implementation as sensing modalities. This is particularly true for sensing assemblies that are to be used as the basis for real time intracellular sensing of intracellular processes and events. We use a quantum dot (QD) donor -mCherry ac...

In line with the recent development of fragment-based drug design, a new computational method for mapping of small ligand molecules on protein surfaces is proposed. The method uses three-dimensional (3D) spatial distribution functions of the atomic sites of the ligand calculated using the molecular theory of solvation, known as the 3D reference interaction site model (3D-RISM) theory, to identi...

First, Schiff base iminopyridine ligand has been prepared by the condensation between primary amine, dimethylaniline and active carbonyl group of pyridine carboxaldehyde, then related complexes were synthesized in methanol solution. The ligand and metal complexes have been characterized by elemental analysis, UV, IR, 1 H NMR and 13CNMR spectroscopy. The spectroscopic data of metal complexes ind...

this study aims to design some dual-target anticancer candidates, capable to act as an alkylating agent as well as a thymidylate synthase (ts) inhibitor. the designed scaffold is a combination of nucleobase, amino acid and aziridine structures. the candidates are docked into ts and three dna double strand structures and evaluated based on their binding interaction energies and ligand efficienci...

The drug efflux pump P-glycoprotein (P-gp) has been shown to promote multidrug resistance (MDR) in tumors as well as to influence ADME properties of drug candidates. Here we synthesized and tested a series of benzophenone derivatives structurally analogous to propafenone-type inhibitors of P-gp. Some of the compounds showed ligand efficiency and lipophilic efficiency (LipE) values in the range ...