Objective(s): Alzheimer’s disease (AD) as progressive cognitive decline and the most common form of dementia is due to degeneration of the cholinergic neurons in the brain. Therefore, administration of the acetylcholinesterase (AChE) inhibitors such as donepezil is the first choice for treatment of the AD. In the present study, we focused on the synthesis and anti-cholinesterase evaluation of n...

The complex [(PhCH2NC)AuCl], 1, was prepared by the reaction of [(Me2S)AuCl], A, with an equimolar amount of benzyl isocyanide (PhCH2NC) ligand. Through a salt metathesis reaction, the chloride ligand in 1 was replaced by potassium benzothiazole-2-thiolate (Kbt) and potassium benzoimidazole-2-thiolate (Kbi) to a...

Dual-mode surface-plasmon resonance (SPR) sensors use both long- and short- range surface plasmon waves to differentiate surface binding interactions from interfering bulk effects. We have optimized the design of these sensors for minimum surface limit of detection (LOD) using a Cramer-Rao lower bound for spectral shift estimation. Despite trade-offs between resonance width, minimum reflectivit...

Activation of the ERK pathway is a hallmark of cancer, and targeting of upstream signaling partners led to the development of approved drugs. Recently, SCH772984 has been shown to be a selective and potent ERK1/2 inhibitor. Here we report the structural mechanism for its remarkable selectivity. In ERK1/2, SCH772984 induces a so-far-unknown binding pocket that accommodates the piperazine-phenyl-...

This article presents the design of a sequence-based predictor named ProteDNA for identifying the sequence-specific binding residues in a transcription factor (TF). Concerning protein-DNA interactions, there are two types of binding mechanisms involved, namely sequence-specific binding and nonspecific binding. Sequence-specific bindings occur between protein sidechains and nucleotide bases and ...

The optical response, binding parameters, and duplex DNA binding mode of water-soluble kinetically inert tetranuclear metallomacrocycles can all be controlled by judicious selection of ancillary ligands.

The binding of three closely related chelators: 5-hydroxy-2-methyl-4H-pyran-4-thione (allothiomaltol, ATM), 3-hydroxy-2-methyl-4H-pyran-4-thione (thiomaltol, TM), and 3-hydroxy-4H-pyran-4-thione (thiopyromeconic acid, TPMA) to the active site of human carbonic anhydrase II (hCAII) has been investigated. Two of these ligands display a monodentate mode of coordination to the active site Zn(2+) io...

Two sets of ligand binding decoys have been constructed for the community structure-activity resource (CSAR) benchmark by using the MDock and DOCK programs for rigid- and flexible-ligand docking, respectively. The decoys generated for each complex in the benchmark thoroughly cover the binding site and also contain a certain number of near-native binding modes. A few scoring functions have been ...

Actinomycin D (ActD) is a small molecule with strong antibiotic and anticancer activity. However, its biologically relevant DNA-binding mechanism has never been resolved, with some studies suggesting that the primary binding mode is intercalation, and others suggesting that single-stranded DNA binding is most important. To resolve this controversy, we develop a method to quantify ActD's equilib...

Figure 1. NOS inhibitors. X-ray structures of 6 inhibitors bound to iNOS (a-c) and eNOS (d) representative of three different pharmacophores used in this study. (a) Binding mode of small (1) and large (3) quinazolines to iNOS. (b) Binding mode of small (6) and large (9) aminopyridines to iNOS. (c) Binding mode of small (14) and large (16) bicyclic thienooxazepines to iNOS. Binding of the large ...