Original Data for “Relationship between deformation and temperature in a subduction zone: examples from accretionary and high-P/T metamorphic complexes on the central Kii Peninsula, SW Japan”

This is the original data for “Relationship between deformation and temperature in a subduction zone: examples from accretionary and high-P/T metamorphic complexes on the central Kii Peninsula, SW Japan”, including five Excel datasheet files

Anti-Markovnikov Hydroheteroarylation of Unactivated Alkenes with Indoles, Pyrroles, Benzofurans, and Furans Catalyzed by a Nickel–<i>N</i>‑Heterocyclic Carbene System

We report the catalytic addition of C–H bonds at the C2 position of hetero­arenes, including pyrroles, indoles, benzofurans, and furans, to unactivated terminal and internal alkenes. The reaction is catalyzed by a combination of Ni­(COD)₂ and a sterically hindered, electron-rich <i>N</i>-hetero­cyclic carbene ligand or its analogous Ni­(NHC)­(arene) complex. The reaction is highly selective for anti-Markovnikov addition to α-olefins, as well as for the formation of linear alkylheteroarenes from internal alkenes. The reaction occurs with substrates containing ketones, esters, amides, boronate esters, silyl ethers, sulfon­amides, acetals, and free amines

Synthesis and Antimuscarinic Properties of Quinuclidin-3-yl 1,2,3,4-Tetrahydroisoquinoline-2-carboxylate Derivatives as Novel Muscarinic Receptor Antagonists

In the course of continuing efforts to develop potent and bladder-selective muscarinic M3 receptor antagonists, quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives and related compounds were designed as conformationally restricted analogues of quinuclidin-3-yl benzhydrylcarbamate (8). Binding assays with rat muscarinic receptor subtypes revealed that the quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives showed high affinities for the M3 receptor, and selectivity for the M3 receptor over the M2 receptor. Of these derivatives, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride (9b) exhibited almost the same inhibitory activity against bladder contraction to that of oxybutynin (1), and more than 10-fold selectivity for bladder contraction versus salivary secretion, demonstrating that 9b may be useful for the treatment of symptoms associated with overactive bladder without having side effects such as dry mouth

Spongistatin Synthetic Studies. An Efficient, Second-Generation Construction of an Advanced ABCD Intermediate

A short, efficient, and stereocontrolled synthesis of (−)-4, an advanced ABCD subunit of the spongistatins, has been achieved. Central to the synthetic strategy is the multicomponent linchpin union of silyl dithianes with epoxides to access both the AB and CD fragments. Fragment coupling was then achieved via an efficient stereoselective aldol reaction. The linear sequence required 22 steps and proceeded in 4.0% overall yield

'Beskrifning på et nytt Örtegenus'

The refolding of cysteine-free pyrrolidone carboxyl peptidase (PCP-0SH) from a hyperthermophile is unusually slow. PCP-0SH is trapped in the denatured (D1) state at 4 °C and pH 2.3, which is different from the highly denatured state in the presence of concentrated denaturant. In order to elucidate the mechanism of the unusually slow folding, we investigated the structure of the D1 state using NMR techniques with amino acid selectively labeled PCP-0SH. The HSQC spectrum of the D1 state showed that most of the resonances arising from the 114–208 residues are broadened, indicating that conformations of the 114–208 residues are in intermediate exchange on the microsecond to millisecond time scale. Paramagnetic relaxation enhancement data indicated the lack of long-range interactions between the 1–113 and the 114–208 segments in the D1 state. Furthermore, proline scanning mutagenesis showed that the 114–208 segment in the D1 state forms a loosely packed hydrophobic core composed of α4- and α6-helices. From these findings, we conclude that the 114–208 segment of PCP-0SH folds into a stable compact structure with non-native helix–helix association in the D1 state. Therefore, in the folding process from the D1 state to the native state, the α4- and α6-helices become separated and the central β-sheet is folded between these helices. That is, the non-native interaction between the α4- and α6-helices may be responsible for the unusually slow folding of PCP-0SH

Structural Characterization of a Trapped Folding Intermediate of Pyrrolidone Carboxyl Peptidase from a Hyperthermophile

The refolding of cysteine-free pyrrolidone carboxyl peptidase (PCP-0SH) from a hyperthermophile is unusually slow. PCP-0SH is trapped in the denatured (D1) state at 4 °C and pH 2.3, which is different from the highly denatured state in the presence of concentrated denaturant. In order to elucidate the mechanism of the unusually slow folding, we investigated the structure of the D1 state using NMR techniques with amino acid selectively labeled PCP-0SH. The HSQC spectrum of the D1 state showed that most of the resonances arising from the 114–208 residues are broadened, indicating that conformations of the 114–208 residues are in intermediate exchange on the microsecond to millisecond time scale. Paramagnetic relaxation enhancement data indicated the lack of long-range interactions between the 1–113 and the 114–208 segments in the D1 state. Furthermore, proline scanning mutagenesis showed that the 114–208 segment in the D1 state forms a loosely packed hydrophobic core composed of α4- and α6-helices. From these findings, we conclude that the 114–208 segment of PCP-0SH folds into a stable compact structure with non-native helix–helix association in the D1 state. Therefore, in the folding process from the D1 state to the native state, the α4- and α6-helices become separated and the central β-sheet is folded between these helices. That is, the non-native interaction between the α4- and α6-helices may be responsible for the unusually slow folding of PCP-0SH

â or no â: Complex optical superposition states

<p>Poster presented at the International Conference on Quantum Information and Technology (ICQIT) in Tokyo, October 2010.</p> <p>This poster covers our experiment on preparation of arbitrary superpositions (qubits) of squeezed vacuum and squeezed single-photon states. The method we used was indistinguishable photon subtraction from an initial squeezed vacuum or from an independent coherent state.</p> <p>The results were published in Physical Review Letters 105, 053602 (2010) and Journal of Modern Optics 58, 266-275 (2011).</p

Structural Characterization of a Trapped Folding Intermediate of Pyrrolidone Carboxyl Peptidase from a Hyperthermophile

The refolding of cysteine-free pyrrolidone carboxyl peptidase (PCP-0SH) from a hyperthermophile is unusually slow. PCP-0SH is trapped in the denatured (D1) state at 4 °C and pH 2.3, which is different from the highly denatured state in the presence of concentrated denaturant. In order to elucidate the mechanism of the unusually slow folding, we investigated the structure of the D1 state using NMR techniques with amino acid selectively labeled PCP-0SH. The HSQC spectrum of the D1 state showed that most of the resonances arising from the 114–208 residues are broadened, indicating that conformations of the 114–208 residues are in intermediate exchange on the microsecond to millisecond time scale. Paramagnetic relaxation enhancement data indicated the lack of long-range interactions between the 1–113 and the 114–208 segments in the D1 state. Furthermore, proline scanning mutagenesis showed that the 114–208 segment in the D1 state forms a loosely packed hydrophobic core composed of α4- and α6-helices. From these findings, we conclude that the 114–208 segment of PCP-0SH folds into a stable compact structure with non-native helix–helix association in the D1 state. Therefore, in the folding process from the D1 state to the native state, the α4- and α6-helices become separated and the central β-sheet is folded between these helices. That is, the non-native interaction between the α4- and α6-helices may be responsible for the unusually slow folding of PCP-0SH

Characterization of the Denatured Structure of Pyrrolidone Carboxyl Peptidase from a Hyperthermophile under Nondenaturing Conditions: Role of the C-Terminal α-Helix of the Protein in Folding and Stability^†^,^‡

The cysteine-free pyrrolidone carboxyl peptidase (PCP-0SH) from a hyperthermophile, Pyrococcus furiosus, can be trapped in the denatured state under nondenaturing conditions, corresponding to the denatured structure that exists in equilibrium with the native state under physiological conditions. The denatured state is the initial state (D1 state) in the refolding process but differs from the completely denatured state (D2 state) in the concentrated denaturant. Also, it has been found that the D1 state corresponds to the heat-denatured state. To elucidate the structural basis of the D1 state, H/D exchange experiments with PCP-0SH were performed at pD 3.4 and 4 °C. The results indicated that amide protons in the C-terminal α6-helix region hardly exchanged in the D1 state with deuterium even after 7 days, suggesting that the α6-helix (from Ser188 to Glu205) of PCP-0SH was stably formed in the D1 state. In order to examine the role of the α6-helix in folding and stability, H/D exchange experiments with a mutant, A199P, at position 199 in the α6-helix region were performed. The α6-helix region of A199P in the D1 state was partially unprotected, while some hydrophobic residues were protected against the H/D exchange, although these hydrophobic residues were unprotected in the wild-type protein. These results suggest that the structure of A199P in the D1 state formed a temporary stable denatured structure with a non-native hydrophobic cluster and the unstructured α6-helix. Both the stability and the refolding rate decreased by the substitution of Pro for Ala199. We can conclude that the native-like helix (α6-helix) of PCP-0SH is already constructed in the D1 state and is necessary for efficient refolding into the native structure and stabilization of PCP-0SH

4‑Hydroxypyridazin-3(2<i>H</i>)‑one Derivatives as Novel d‑Amino Acid Oxidase Inhibitors

d-Amino acid oxidase (DAAO) catalyzes the oxidation of d-amino acids including d-serine, a coagonist of the <i>N</i>-methyl-d-aspartate receptor. We identified a series of 4-hydroxypyridazin-3­(2<i>H</i>)-one derivatives as novel DAAO inhibitors with high potency and substantial cell permeability using fragment-based drug design. Comparisons of complex structures deposited in the Protein Data Bank as well as those determined with in-house fragment hits revealed that a hydrophobic subpocket was formed perpendicular to the flavin ring by flipping Tyr224 in a ligand-dependent manner. We investigated the ability of the initial fragment hit, 3-hydroxy-pyridine-2­(1<i>H</i>)-one, to fill this subpocket with the aid of complex structure information. 3-Hydroxy-5-(2-phenylethyl)­pyridine-2­(1<i>H</i>)-one exhibited the predicted binding mode and demonstrated high inhibitory activity for human DAAO in enzyme- and cell-based assays. We further designed and synthesized 4-hydroxypyridazin-3­(2<i>H</i>)-one derivatives, which are equivalent to the 3-hydroxy-pyridine-2­(1<i>H</i>)-one series but lack cell toxicity. 6-[2-(3,5-Difluorophenyl)­ethyl]-4-hydroxypyridazin-3­(2<i>H</i>)-one was found to be effective against MK-801-induced cognitive deficit in the Y-maze