Structural aspects for the recognition of ATP by ribonucleopeptide receptors

A modular structure of ribonucleopeptide (RNP) affords a framework to construct macromolecular receptors and fluorescent sensors. We have isolated ATP-binding RNP with the minimum of nucleotides for ATP binding, in which the RNA consensus sequence is different from those reported for RNA aptamers against the ATP analogues. The three-dimensional structure of the substrate-binding complex of RNP was studied to understand the ATP-binding mechanism of RNP. A combination of NMR measurements, enzymatic and chemical mapping, and nucleotide mutation studies of the RNP-adenosine complex show that RNP interacts with the adenine ring of adenosine by forming a U:A:U triple with two invariant U nucleotides. The observed recognition mode for the adenine ring is different from those of RNA aptamers for ATP derivatives reported previously. The RNP-adenosine complex is folded into a particular structure by formation of the U:A:U triple and a Hoogsteen type A:U base pair. This recognition mechanism was successfully utilized to convert the substrate-binding specificity of RNP from ATP- to GTP-binding with a C(+):G:C triple recognition mode.     

Regional Chest Wall Volume Changes During Various Breathing Maneuvers in Normal Men

Purpose: The purpose of this study is to investigate the regional chest wall volume changes during various breathing maneuvers in normal men with an optical reflectance system (OR), which tracks reflective markers in three dimensions. Methods: Chest wall volume was measured by the OR system [V_L(CW)], and lung volume was measured by hot wire spirometry [V_L(SP)] in 15 healthy men during quiet breathing (QB), during breathing at a rate of 50 tidal breaths/min paced using a metronome (MT: metronome-paced tachypnea), and during a maximal forced inspiratory and expiratory maneuver (MFIE maneuver). Results: There were few discrepancies between V_L(CW) and V_L(SP) for QB and MT. In the MFIE maneuver, however V_L(CW) was often underestimated compared with V_L(SP), particularly during forced maximal expiration, because of pulmonary rib cage volume changes. Furthermore, the regional chest wall volume changes were affected by breathing maneuver alternation. In the pulmonary and abdominal rib cage, inspiratory reserve volume was larger than expiratory reserve volume, respectively, and in the abdomen, expiratory reserve volume was larger than inspiratory reserve volume. Conclusion: Alternation of breathing maneuvers affects regional chest wall volume changes.     

Novel methodology to control the adsorption structure of cationic porphyrins on the clay surface using the "size-matching rule"

Saponite-type clays that have different cation exchange capacities were successfully synthesized by hydrothermal synthesis. The structure and properties were analyzed by X-ray diffraction, X-ray fluorescence, (27)Al NMR, FT-IR, thermogravimetric and differential thermal analysis, atomic force microscopy, and cation exchange capacity measurement. The intercharge distances on the synthetic saponite (SS) surfaces were calculated to be 0.8-1.9 nm on the basis of a hexagonal array. The complex formation behavior between SS and cationic porphyrins was examined. It turns out that the average intermolecular distance between porphyrin molecules on the SS surface can be controlled, depending on the charge density of the SS. In the case of tetrakis(1-methylpyridinium-4-yl)porphyrin (H(2)TMPyP(4+)), the average intermolecular distances on the SS surface can be controlled from 2.3 to 3.0 nm on the basis of a hexagonal array. It was also found that absorption maxima of porphyrins depend on the charge density of the SS. The adsorption behavior of porphyrin on the SS surface can be rationally understood by the previously reported "size-matching rule". This methodology using host-guest interaction can realize a unique adsorption structure control of the porphyrin molecule on the SS surface, where the gap distance between guest porphyrin molecules is rather large. These findings will be highly valuable to construct photochemical reaction systems such as energy transfer in the complexes.     

Supramolecular organization of light-harvesting porphyrin macrorings

Porphyrin‐based supramolecular nanostructures have been produced by the self‐assembly of porphyrin macrorings with three benzoic acid groups (Acid‐R) on each side of the rings through cooperative carboxyl–carboxyl hydrogen bonds. Structures of the organized Acid‐R were analyzed by AFM, and two clear distribution peaks were observed at 3 and 27 nm in the height‐distribution histogram. From the overall assessment, the higher objects are considered to be one‐dimensional structures standing vertically on the mica substrate. The height corresponds to an 11‐mer of a unit Acid‐R. Light‐harvesting functions were examined by using fluorescence titration, whereby an energy‐acceptor molecule (Tripod 2 ) was employed that strongly interacted with Acid‐R units (association constant: 2.0×10⁸ M ^?1), specifically from the inner pore. The titration results showed that the apparent stoichiometry [Tripod 2 ]/[Acid‐R] was <0.5, and that the value was concentration dependent. Titration results reasonably account for the scheme in which Tripod 2 only interacts with each terminal in the organized Acid‐R. The number of organization was fitted to a 10‐mer of Acid‐R in a 6.8×10^?7 M solution, and was consistent with that estimated from the AFM results. In the composites of organized Acid‐R/Tripod 2 , a singlet excitation energy transfer occurred among the Acid‐R units, and to Tripod 2 . The energy‐transfer rate constants were estimated by using the decamer model, which employed kinetic parameters obtained from steady‐state and time‐resolved fluorescence experiments.     

Size of elementary clusters and process period in silver nanoparticle formation

The time dependence of small-angle X-ray scattering (SAXS) curves for silver nanoparticle formation was followed in situ at a time resolution of 0.18 ms, which is 3 orders of magnitude higher than that used in previous reports (ca. 100 ms). The starting materials were silver nitrate solutions that were reacted with reducing solutions containing trisodium citrate. The SAXS analyses showed that silver nanoparticles were formed in three distinct periods from a peak diameter of ca. 0.7 nm (corresponding to the size of a Ag(13) cluster) during the nucleation and the early growth period. The Ag(13) clusters are most likely elementary clusters that agglomerate to form silver nanoparticles.     

Polycyclic N‐heterocyclic compounds. Part 66: Synthesis of N‐[2‐([1,2,4]oxadiazol‐5‐yl)cyclopenten‐1‐yl]formamide oximes and their evaluation as inhibitors of platelet aggregation

N‐[2‐([1,2,4]Oxadiazol‐5‐yl)cyclopenten‐1‐yl]formamide oximes were synthesized by fusion of (6,7‐dihydro‐5H‐cyclopenta[1,2‐d]pyrimidin‐4‐yl)amidines and/or their amide oximes with hydroxylamine hydrochloride through a subsequent rearrangement reaction. Assay of the products for anti‐platelet aggregation activity revealed that certain of them showed promising inhibitory effect on arachidonic acid‐induced platelet aggregation. J. Heterocyclic Chem., (2011).     

Polycyclic N‐Heterocyclic Compounds. Part 82: Synthesis and Evaluation of Anti‐Platelet Aggregation Activity of 2,4‐Disubstituted 5,6‐Dihydro[1]benzothiepino[5,4‐d]pyrimidine and Related Compounds

We have synthesized a large number of tricyclic 2‐substituted 4‐alkylamino‐5,6‐dihydro[1]benzothiepino[5,4‐d]pyrimidines as part of our research to develop new effective anti‐platelet drugs. A variety of alkyl and aryl groups were used as substituents at the 2‐position. Evaluation of the effects of the newly synthesized compounds on collagen‐induced platelet aggregation revealed several promising anti‐platelet candidates with potencies superior to aspirin.