Biomedical subjects
Publications and source records attributed to Yuichiro Mori.
We have developed an effective microfluidic system for hydrogenation reactions in scCO(2); the reactions proceeded very rapidly (within 1 second), by making the best use of scCO(2) and utilizing the large specific interfacial area of the microchannel reactor, and high reaction productivity was attained in each channel.
We detected non-specific reactions in the measurement of (1-->3)-beta-D-glucan levels (beta-glucan) in plasma, and the influences of the non-specific reactions on sensitivity and specificity of measurement methods were examined. In this study, 460 plasma samples from 174 patients at Kawasaki Medical School Hospital were used, and the plasma beta-glucan levels were measured by different four methods. The methods included the dilution-heating-endpoint (DHE), dilution-heating-turbidimetric (DHT), alkaline-kinetic (AK), and alkaline-endpoint method (AE) with and without 4-amidinophenyl benzoate hydrochloride (APB) of a protease inhibitor blocking the Limulus reaction. Non-specific reactions were detected from the calculated value under conditions with APB. Therefore, both of the actual values and the values equivalent to non-specific reactions were calculated. The incidence of non-specific reactions was 2.4% in DHE method, 0% in DHT, 53.3% in AK, and 99.3% in AE. The sensitivity and specificity in the methods were 35.7% and 96.0%, 28.6% and 96.0%, 78.6% and 80.1%, and 57.1% and 84.1%, respectively. When subtracted the non-specific reaction values from the actual values in AK and AE method, the specificity was increased by 91.4% and 94.0%, respectively. In these two methods, the non-specific reaction was considered to be a major cause of the low specificity. Finally, to measure plasma beta-glucan levels accurately, non-specific reactions should be excluded as possible by further improvement of measurement methods.
We have developed an efficient method for the asymmetric synthesis of anti-beta-hydroxy-alpha-amino acid derivatives based on highly enantio- and diastereoselective aldol reactions of the silicon enolate derived from N-trifluoroacetylglycinate with aldehydes using a chiral zirconium catalyst. The resulting N-trifluoroacetyl group is easily cleaved under either acidic or basic conditions and can be used directly as a protecting group for further transformations.
We have developed an efficient system for triphase reactions using a microchannel reactor. Using this system, we conducted hydrogenation reactions that proceeded smoothly to afford the desired products quantitatively within 2 minutes for a variety of substrates. The system could also be applied to deprotection reactions. We could achieve an effective interaction between hydrogen, substrates, and a palladium catalyst using extremely large interfacial areas and the short path required for molecular diffusion in the very narrow channel space. This concept could be extended to other multiphase reactions that use gas-phase reagents such as oxygen and carbon dioxide.
Large-scale synthesis, design, and structure-activity relationships of khafrefungin are reported. Khafrefungin is an antifungal agent that inhibits inositol phosphorylceramide (IPC) synthase, an enzyme involved in fungal sphingolipid biosynthesis. Unlike other inhibitors that inhibit the corresponding enzyme in fungi and mammals to the same extent, khafrefungin does not impair sphingolipid synthesis in mammals. We have developed an efficient method for large-scale synthesis of khafrefungin, and various khafrefungin derivatives were synthesized based on this method. While most of the khafrefungin derivatives lost antifungal activity, a lactone-type derivative had almost the same activity as khafrefungin. We also designed and synthesized derivatives which contain a five- or six-membered ring at the central part of the structure based on NOE experiments of khafrefungin. A macrocyclic khafrefungin derivative was also synthesized, but the antifungal activity was lost. These results suggest that the structure of khafrefungin might be strictly recognized in fungi.
Colletotrichum lagenarium is a plant pathogenic fungus, and produces melanin that is an essential factor for appressorial penetration into host tissues. The melanin biosynthesis pathway of C. lagenarium starts with pentaketide synthesis catalyzed by polyketide synthase Pks1p. We previously confirmed that the direct product of Pks1p is 1,3,6,8-tetrahydroxynaphthalene. Thus, melanin biosynthesis in this fungus requires the reduction of 1,3,6,8-tetrahydroxynaphthalene to scytalone. We made a double mutant 9141-144 from the thr1 mutant 9141 that lacks the ability to metabolize 1,3,8-trihydroxynaphthalene. The double mutant 9141-144 could metabolize neither 1,3,6,8-tetrahydroxynaphthalene nor 1,3,8-trihydroxynaphthalene. However melanin production by the double mutant was restored by THR1, indicating that Thr1p can metabolize both compounds in vivo. These results demonstrate that two enzymes, Thr1p and a deduced 1,3,6,8-tetrahydroxynaphthalene-specific reductase, are involved in the first reduction step of the melanin biosynthesis pathway of C. lagenarium.
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