Osamu Ichihara

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Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains(More)
Polystyrene-poly(ethylene glycol) resin-captured cross-linked palladium nanopaticles were prepared via a straightforward route, and their heterogeneous behavior was truly confirmed by various tests. They were applied to aqueous Suzuki cross-coupling reactions with various aryl bromides and recycled up to six times without loss of activity.
Using a computational approach to assess changes in solvation thermodynamics upon ligand binding, we investigated the effects of water molecules on the binding energetics of over 20 fragment hits and their corresponding optimized lead compounds. Binding activity and X-ray crystallographic data of published fragment-to-lead optimization studies from various(More)
A new series of potent TG2 inhibitors are reported that employ a 4-aminopiperidine core bearing an acrylamide warhead. We establish the structure-activity relationship of this new series and report on the transglutaminase selectivity and in vitro ADME properties of selected compounds. We demonstrate that the compounds do not conjugate glutathione in an in(More)
A furanose sugar amino acid (SAA) has been utilized as a library scaffold for the first time. Two furanose SAA scaffolds were examined to illustrate their potential for derivatization. The resulting 99-member library contained three orthogonal points of diversification that allowed easy access to ethers and carbamates from a hydroxyl moiety, a range of(More)
BACKGROUND The reliable and robust estimation of ligand binding affinity continues to be a challenge in drug design. Many current methods rely on molecular mechanics (MM) calculations which do not fully explain complex molecular interactions. Full quantum mechanical (QM) computation of the electronic state of protein-ligand complexes has recently become(More)
The linking together of two fragment compounds that bind to distinct protein sub-sites can lead to a superadditivity of binding affinities, in which the binding free energy of the linked fragments exceeds the simple sum of the binding energies of individual fragments (linking coefficient E<1). However, a review of the literature shows that such events are(More)
Driven by a steady improvement of computational hardware and significant progress in ab initio method development, quantum-mechanical approaches can now be applied to large biochemical systems and drug design. We review the methods implemented in GAMESS, which are suitable to calculate large biochemical systems. An emphasis is put on the fragment molecular(More)
Long-chain fatty acids (FAs) with low water solubility require fatty-acid-binding proteins (FABPs) to transport them from cytoplasm to the mitochondria for energy production. However, the precise mechanism by which these proteins recognize the various lengths of simple alkyl chains of FAs with similar high affinity remains unknown. To address this question,(More)