A potent immunosuppressive activity was found in the culture broth of the fungus Isaria sinclairii (ATCC 24400). The metabolite, ISP-I ((2JS,3^,4^)-(j&)-2-amino-3,4-dihydroxy-2-hydroxymethyl-14-oxoeicos-6-enoic acid, myriocin = thermozymocidin) suppressed the proliferation of lymphocytes in mouse allogeneic mixed lymphocyte reaction, but had no effect on the growth of humantumor cell lines. It also suppressed the appearance of plaque-forming cells in response to sheep red blood cells and the generation of allo-reactive cytotoxic T lymphocytes in mice after intraperitoneal or oral administration.The metabolite was 10-to 100-fold more potent than cyclosporin A as an immunosuppressiveagent of the immuneresponse in vitro and in vivo, and appears to be a candidate for clinical application as a powerful immunosuppressant.

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A series of 2-substituted 2-aminopropane-1,3-diols was synthesized and evaluated for their lymphocyte-decreasing effect and immunosuppressive effect on rat skin allograft. A phenyl ring was introduced into the alkyl chain of the lead compound 3, which is an immunosuppressive agent structurally simplified from myriocin (1, ISP-I) via compound 2. The potency of the various compounds was dependent upon the position of the phenyl ring within the alkyl side chain. The most suitable length between the quaternary carbon atom and the phenyl ring was two carbon atoms. 2-Substituted 2-aminoethanols were successively synthesized and evaluated for their T-cell-decreasing effect and immunosuppressive effect using a popliteal lymph node gain assay in rats. The absolute configuration at the quaternary carbon affected the activity, and the (pro-S)-hydroxymethyl group of compound 6 was essential for potent immunosuppressive activity. Favorable substituents for the (pro-R)-hydroxymethyl group of 6 were hydroxyalkyl (hydroxyethyl and hydroxypropyl) or lower alkyl (methyl and ethyl) groups. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride (6, FTY720) was found to possess considerable activity and is expected to be useful as an immunosuppressive drug for organ transplantation.

Several immunosuppressants, ISP-I [(2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoeicos++ +-6-enoic acid, myriocin = thermozymocidin] and mycestericins A-G, were isolated from culture broths of Isaria sinclairii and Mycelia sterilia, respectively. In order to investigate structure-activity relationships, extensive modifications of ISP-I were conducted, and it was established that the fundamental structure possessing the immunosuppressive activity is a symmetrical 2-alkyl-2-aminopropane-1,3-diol. The tetradecyl, pentadecyl, and hexadecyl derivatives prolonged rat skin allograft survival in the combination of LEW donor and F344 recipient and were more effective than cyclosporin A. Among them, 2-amino-2-tetradecylpropane-1,3-diol hydrochloride, ISP-I-55, showed the lowest toxicity. ISP-I-55 is a promising lead compound for the development of effective immunosuppressants for organ transplantations and for the treatment of autoimmune diseases.

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Temperature dependent recombination dynamics in InP/ZnS colloidal nanocrystals Appl. Phys. Lett. 101, 091910 (2012) Intrinsic defect in BiNbO4: A density functional theory study J. Appl. Phys. 112, 043706 (2012) The CuInSe2-CuIn3Se5 defect compound interface: Electronic structure and band alignment Appl. Phys. Lett. 101, 062108 (2012) Investigation of deep-level defects in conductive polymer on n-type 4H-and 6H-silicon carbide substrates using I-V and deep level transient spectroscopy techniquesMajor deep levels observed in as-grown and irradiated n-type 4H-SiC and 6H-SiC epilayers have been investigated. After low-energy electron irradiation, by which only carbon atoms are displaced, five traps, EH1 ͑E C − 0.36 eV͒, Z 1 / Z 2 ͑E C − 0.65 eV͒, EH3 ͑E C − 0.79 eV͒, EH5 ͑E C − 1.0 eV͒, and EH6/7 ͑E C − 1.48 eV͒, were detected in 4H-SiC and four traps, E 1 / E 2 ͑E C − 0.45 eV͒, RD 5 ͑E C − 0.57 eV͒, ES ͑E C − 0.80 eV͒, and R ͑E C − 1.25 eV͒, were detected in 6H-SiC. The Z 1 / Z 2 , EH6/7 centers in 4H-SiC and the E 1 / E 2 , R centers in 6H-SiC exhibit common features as follows: their generation rates by the e − -irradiation were almost the same each other, their concentrations were not changed by heat treatments up to 1500°C, and they showed very similar annealing behaviors at elevated temperatures. Furthermore, these defect centers were almost eliminated by thermal oxidation. Taking account of the observed results and the energy positions, the authors suggest that the Z 1 / Z 2 center in 4H-SiC corresponds to the E 1 / E 2 center in 6H-SiC, and the EH6/7 center in 4H-SiC to the R center in 6H-SiC, respectively. Since the concentrations of these four centers are almost the same for as-grown, electron-irradiated, annealed, and oxidized samples, these centers will contain a common intrinsic defect, most likely carbon vacancy. The authors also observed similar correspondence for other thermally unstable traps in 4H-SiC and 6H-SiC.