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91.
Komatsu T Ohmichi N Zunszain PA Curry S Tsuchida E 《Journal of the American Chemical Society》2004,126(44):14304-14305
Human serum albumin (HSA) is the most abundant plasma protein in our bloodstream and serves as a transporter for small hydrophobic molecules such as fatty acids, bilirubin, and steroids. Hemin dissociated from methemoglobin is also bound within a narrow D-shaped cavity in subdomain IB of HSA. In terms of the general hydrophobicity of the alpha-helical pocket, HSA potentially has features similar to the heme-binding site of myoglobin (Mb) or hemoglobin (Hb). However, the reduced ferrous HSA-heme complex is immediately oxidized by O2, because HSA lacks the proximal histidine that enables the heme group to bind O2. In this paper, we report the introduction of a proximal histidine into the subdomain IB of HSA by site-directed mutagenesis to construct a tailor-made heme pocket (I142H/Y161L), which allows a reversible O2 binding to the prosthetic heme group. Laser flash photolysis experiments revealed that this artificial hemoprotein appears to have two different geometries of the axial-imidazole coordination, and these two species (I and II) showed rather low O2 binding affinities (P1/2O2 = 18 and 134 Torr) relative to those of Mb and Hb. 相似文献
92.
Hirobumi Takahashi Takehiro Fukami Hisaki Kojima Takeru Yamakawa Hiroyuki Takahashi Toshihiro Sakamoto Teruyuki Nishimura Masayuki Nakamura Takashi Yosizumi Kenji Niiyama Norikazu Ohtake Takashi Hayama 《Tetrahedron》2005,61(14):3473-3481
A robust synthetic method for 2-alkylamino-6-carboxy-5,7-diarylcyclopenteno[1,2-b]pyridines via acylamination at the alpha position of the functionalized pyridine system has been developed. The key step in this method was achieved by treatment of the corresponding pyridine N-oxides with 2.5 equiv of imidoyl chlorides in the presence of triethylamine, thus producing the desired 2-acylaminopyridines in good yields (74-96%). 相似文献
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94.
Hiromitsu Kozuka 《Journal of Sol-Gel Science and Technology》2011,57(3):231-232
Editorial Note
2009 ISGS life achievement award 相似文献95.
Hiroyuki Shinoda Michio Sayama Masa-Aki Mori Hiroshi Kozuka 《International journal of quantum chemistry》1993,45(1):97-104
Hydration to the aldehyde group in nitro-substituted benzaldehydes was studied theoretically by using an AM 1 method. The calculated values of activation energy and heat of reaction showed good correlations with the experimental values of rate constants and equilibrium constants, respectively. To examine the hydration mechanism, localized molecular orbitals were calculated. Furthermore, expression of the molecular orbitals of supermolecular complexes in terms of occupied and vacant orbitals of the component molecules elucidated that the interaction between the lonepair orbital of water and the antibonding C? O π-orbital of aldehyde was important. 2,6-DNBAl was concluded to be less reactive toward water than was 2.4-DNBAl. This is consistent with the experimental result that the mutagenic activity of 2,4-DNBAl depends not only on the reduction of the nitro group by a bacterial enzyme but also on the acetyl conjugation, but that in the case of 2,6-DNBAl the mutagenic activity is manifested through the reduction by a bacterial enzyme. © 1993 John Wiley & Sons, Inc. 相似文献
96.
97.
FK888 (NK1 antagonist) is a candidate drug for migraine and selected as a model of amorphous drug. FK888 was micronized to develop as dry powder inhalers (DPIs) taking into consideration of its water insoluble property. The glass transition temperature (Tg) and fragility (m) were 90 degrees C and 118, respectively, and it was categorized as a fragile glass based on Angell's concept. FK888 was structurally relaxed by aging below Tg, then the effect of aging on their physical and aerosol properties were investigated. The investigation on the moisture sorption-desorption isotherms of FK888 indicated that aged FK888 adsorbed less amount of water than that of unaged FK888. This unique moisture sorption-desorption behavior of the aged sample is explained by structural relaxation accompanying decrease of free volume and/or increase of density. As for the dissolution rate of unaged and aged FK888, they showed the similar value, suggesting that there would be no difference in bioavailability. In relation to the stability, FK888 DPIs prepared by unaged and aged FK888 were stored at 70 degrees C, and the respirable fraction of FK888 DPIs was evaluated by using multistage cascade impactor (USP apparatus 3). As a result, the respirable fraction of FK888 DPIs prepared by unaged sample was significantly decreased compared to the aged sample, suggesting that agglomeration may occur in the unaged sample during the storage. This phenomenon was supported by that the unaged sample showed a significant decrease in the surface area compared to that of the aged sample when stored at various conditions. 相似文献
98.
99.
100.
In order to investigate the excretion and distribution of 2,4-DNT in the rat, 3H-2,4-DNT was synthesized by nitration reaction of 3H-toluene. About 21.3 per cent of the single orally administered radioactivity was excreted in the 1st day-faeces. The amounts of radioactivity in the 2nd day- and 3rd day-faeces were to be about 4.1 and 1.1 per cent, respectively. About 13.5 per cent of the radioactivity administered was excreted in the 1st day-urine, but after the 2nd day the excretion of radioactivity was to be trace. In all, about 46 per cent of the radioactivity administered was excreted in the faeces and urine during the 7 days. Seven days after administration relatively high levels of radioactivity were retained in adipose tissue, skin, and liver, however, the amounts of remaining radioactivity were to be only 1.5, 0.6 and 0.4 per cent, respectively. The amounts of radioactivity of the other organs were to be trace. 相似文献