- PDF 無料ダウンロード

Size: px

Start display at page:

Download ""

まいかはにうだ
5 years ago
Views:

3 (Quality of Life; QL) QL (Nerve Growth Factor; NGF) NGF PC12 6- (6-HITC)

4 NGF NGF NGF PTP1B 6-HITC PTP1B NGF PTP1B 6-HITC PTP1B 6-HITC NGF 6-HITC 6-HITC in vivo Tel:

7 20-Hydroxyecdysone Dibenzoylhydrazine

11 ABA 1960 ABA ABA ABA ABA ABA ABA ABA ABA ABA ABA ABA 8'- P450 ABA ABA

12 ABA ABA ABA 8' TEL&FAX

16 NH PP N R H H HH NH H P P N H H HH R UDP H AcHN H H H H H H H H C - H H AcHN H P P - - AcHN H H H P - NH N HH P - NH N HH UDP-LacNAc Kobata, J. Biochem., 53, 167 (1963). UDP-Neu5AcLacNAc Jourdian et al., Fed. Proc., 20, 161 (1961). UDP j @guedu.cc.gifu-u.ac.jp Tel :

17 Flammulina velutipes F. velutipes PCR fluorescence differential display (FDD) 10 RNA FDD cdna accession No. AB AB northern blot BLASTX 29 cdna GTP-binding protein growth factor ubiqutin-proteasome cytochrome P450 hydrophobin polysaccharide deacetylase

18 Fluorescence Differential Disply

Wild-type rsp5 mutant YPD 25 YPD 37 SD 37 Ubiquitination Ub Ub Growth No Ubiquitination Growth inhibition Rsp5 Ub Ub Ub Abnormal proteins Degradation in proteasome or vacuole rsp5 Ub Abnormal

20 Wild-type rsp5 mutant YPD 25 YPD 37 SD 37 Ubiquitination Ub Ub Growth No Ubiquitination Growth inhibition Rsp5 Ub Ub Ub Abnormal proteins Degradation in proteasome or vacuole rsp5 Ub Abnormal proteins accumulation Wild-type rsp5 mutant + Temp. up-shift + Sorbitol + Ethanol Wild-type Time min HSP12 ACT1 rsp5 mutant Time min Wild-type rsp5 mutant V H M V H -HA western -Pgk1 western M Hsf1 Msn4 Pgk1 Golgi ER proteasome Ub Ub Rsp5 Ubiquitination? Hsf1 HSE Ub Hsf1 Msn2/4 STRE Ub Msn2/4 Transport? Nucleus Induction HSP42, HSP12, DDR2

21 Figure 1 H 3 S H NH2 R Me N H N NH H 2 C N Me H H 1a: Liposidomycin A : R= Me (CH 2 ) 3 1b: Liposidomycin B : R= 1c: Liposidomycin C : R= CH 2 Me 2 (CH 2 ) 8 Me(CH 2 ) 10 H H 2 C N Me Me N H H N H degradation product (2) NH

22 Figure 2 Me H N H N H 2 C N Me H H 2 NH Me Bz N Bn N Ph N Me Ac Ac 3 NH Ph NH Me 4 + H N 3 5 Bn Me H Bz H Ph N Me H D-ribose Me N 7 H Bn 5 Me (CCl) 2, DIPEA CH 2 Cl 2 4 (11steps 20% from D-ribose) 2 steps 41% Bz Ph Me Ph N Me N N 3 6 Ac 8 Bn Me N Bn Ac Ac Me 7steps 11% TMS N N SnCl 4 9 TMS 3 Figure 3 Bn Ac N Bn 4 steps 9,SnCl 4 N NH N 37% Ns 55% R Ac Ac Ac Ac Bn N Me 10 11: R=Ns 13 12: R=CH Bz R R N Bn N Bn Bz Ac N NH Ph N Ph N Me Ac Ac Me Ac Ac 14 R=Ns or CH 15 N NH 3 2

23 ( TGase TGase 8 TGase 1, 3 Factor XIII TGase 2 TGase TGase TGase M13 piii N 12 TGase

24 TGase TGase 2 Factor XIII TGase N

26 - (Caco-2 ) (HepG2 ) I-I-A-E-K ( ) Ile Ile Ala Glu Lys Biochem. Biophys. Res. Commun. 281, (2001)

27 (RAS) (ACE) RAS D R V Y I H P F H L V D R V Y I H P F H L D R V Y I H P F RAS 10 ACE Na His P5 -Pro P4 -Phe P3 (HPF)

28 1) HPF HPF (VA) WSZ1a BSZ4 8 RADHPF( III) ADHPFLFLIK(VA-X ) ADHPFLFFIR(VA-Y ) DHPFLFLV HPFLFLVR(WSZ1a ) VANHPFLFLIRVANHPFLFLIR(BSZ4 ) (TRX)C (TRX- ) BL21(DE3) TRX TRX (300 µm) TRX 100 TRX-ADHPFLFLIKTRX-ADHPFLFFIR TRX-DHPFLFLVTRX-HPFLFLVRTRX-VANHPFLFLIR TRX-ADHPFLFLIKTRX-ADHPFLFFIRTRX-DHPFLFLVTRX-HPFLFLVR TRX-VANHPFLFLIR(300 µm) IC µm TRX-VANHPFLFLIR Ki 53 µm TRX-RADHPFTRX-VANHPFTRX-LFLIR(300 µm) HPF C () () 1) 2002 p. 123

31 γ [ ] 3 ATP 2 γ GCS γ 2 γ GCS

32 GCS buthionine sulfoximine(bs) BS GCS GCS BS GCS BS X [ ] GCSBSMgADP PEG10,000 X SPring-8 BL40B2 2.3Å P21 a=70.5 Å, b=97.6 Å, c=102.7 Å, β=109.5 R 21%(Rfree24) GCSBSMgADP ATP γ BS BS TSA GCS α TSA Tyr241 Tyr300 GCS GCSTSA BS Tyr300 Tyr300 BS TSA 500 Tyr300 Tyr241 Tyr241 Tyr241 BS CH-π Tyr241 Gln144

Ł\”ƒ-2005

$Ł\”ƒ-2005$