j j j
FY¢78!C!JN
(http://www.chem.eng.osaka-u.ac.jp/FBC/)
0/ 2
The power of the dream
&4 ^¡!X>E<JN1¡
1/ '.+(%, 3
Q3b`!
j j j j 2/
@|WG_}b!. 4
D#:j nrqjmpvsuuwjlqwqovprjktwxsxyxq¡
_i\V|z{~~T/ 10 j j K]M (!!d)!JNd¡j
3/ $#"! 18 I'5=j c,O!!dA!RJNL¡
"SM j 9!!d6g0L!JNL¡
0% j (+O!!dfB)!JNL¡j
4/ 27
j *~h-aH3[$
?Dj ePL!2Z!d! JNL¡
5/ )&-*) 32 Uj j 9);!CA)!JNL¡
6/ '.+(%, 36
40
î î î The power of the dream
î őÓŒ(I.Ť«b
Pî i+î î î î òŁōŏĺīĪ5(I¤«óĒĔčĐ8 ĖŌĶŐĖRëËĕ:¯|Ĩéûï`ÑõĊăěąð13 S ĖtĖvđˤ«őH(I¤«ï® 23 1ŌĶŐ-ŒùĢæħčĐûĊŇŏĽŐĒăĐïěĊjN ĔõòóĖŇŏĽŐĒăĐāe3ĨéõĊĞĖĒ]õěąð
ěĆtĕ261ĖŌĶŐđĞ,őCŒùĢ´úôģěăĊġöĕSĖ1uĕ± Ė®108ˤ«
ĨvđåąĤĀĒúđûïěĊAýĖlñĕ-$éûïđôčĊĀĒĕÎĖĒăĐ`ÑõĊăěąð òĎýĤ5(IóĨĺŐŅĒăĐÌJăĊ¿pĕėïÀĢú"ÂĒõöâĕØĨ¹ýĒĒĞĕzaÐĪłōŐĸ ĕæħčĐûĊĀĒĖĀċħģĞôģěăĊð
ĀĀ10SģėòĿĻıļņłōijĭįĻóğòÄÕ3000łōijĭįĻóĕÆĒĂĥĤ5²ĨzaąĤH_<
Ĩ¸ºĕÊwąĤdzÞÐĕ;ďý¤«úőAý˰Ĩ üÙĩđŒÜOăĐûěăĊðĈ˵xï¥ùĕĈ ĀĕôĤdzėNăùĤġöĕĔčĐûěăĊðăùăï¡ğIJĴĺņĖÊėēĀěđđûĊĖđăĠö ùð
lđïzaÐĪłōŐĸĨÛĄĊ5IJĴĺņĖÊĖÍĜùĢĞAýĖaxúěĥĐûĐõěąðH ğÕùĢ5IJĴĺņĖÊğYĨ eąĕėĀĥĢˤ«axúcý{ăĂĥĐõýĀĒú[ÇđôĦ öǼ÷ĐõěąðTvS7 u1Ėò(IĒQyóĕßúò5©IĒÕ©IĨĎĔþ(IĒóĒõöR ëËĨsùĥĐøĢĥěăĊúïòŁōŏĺīĪ5(I¤«óėĈĖáÇĔX!ĨxĊąđôĦö]õěąð fģÚčĐÈěąĒ13S ĖtĖvđˤ«őH(I¤«ŒėWoCĖ£ő)àCŒ ĖøÎđ,Fĝï30 /*ĘĨZĕ#ôĚĥĤŇŏĽŐú'ĉĦõăĊĴĶŐĻđăĊðNăèúª ĞčĊçÃĖĕģĔúĢýBĨÏĢĥĤlĕïÀĖÝúēöĔĤĖù¨ÀØĒăĐõĊoĕï ľŎŐĨÔõïěĊ06%ĨéõĐûĊĒ]õěąð
ĈöõöľŎŐĨÁõĕVû¶üïĂĢĕOĂćĐõýĀĒúCđôĤĀĒĕ 1Ė,äĖRëËÛ ģõėôģěćĩð¤«>úCûý?(ăïİōŐĽŋĔ ĕqĂĥĐõĤ¦ĕøõĐĈĥėKnĔ ĀĒđėĔõùĞăĥěćĩð
ĀĖ@Ė)ĮŊŏŀĹįđmvĖEHĵŁĻńŐŋĸŐņė^ìĖãŇķŋĨcĕăěăĊðBĕ4ùčĐ[
ĕ¬Č4ùöGėAýĖ`&Ĩ÷ĐýĥěăĊðòThe power of the dreamóðĀĥėvđˤ«Ė»SĖĪ ĻʼnŏĶĮŊŏŀĹįĖåUđ~ħĥĊrđąúïBĨ#ĕÜĩđõýGė©I½ĕĞÛĖĞĖđăĠöð î î kĊĔĴĺĹłĕ×ĜăĊŁōŏĺīĪ5(I¤«đėVû·ûïSíĨ7ħĆïBĨÏģ2čĐõý
>đôģ·ÿĐ}ăõĒ]õěąðĎĖHïĎĖÒĨMĕÉLąĤïÉąĤïÊąĤĒõö¢hĔ G'đ©Iĕ4û2õïgăïÀĢĖBĨÏĤðĈ˵xĒăĐkĊĔĬļŃŐIJňŏúěĥĤðăĐyï y¤«đėĜćĔõĞĖĨ¾ađûĤ>đôĤĀĒð¤«ėJĖê9ĕdĤĀĒĔý¤«½úoĨ Ö÷ĐïĈöõöG'ĨDöĀĒĔýOăĐõý=đôģ·ÿĤĀĒĨ§\ăĐõěąð
őĔùĄěî ĒăęĦî [email protected]Œ
% )'
*% "!&)' +
*% (+
*% " #$+
*% +
)7p).).^.tiol
200859I18GîJï¤Á20Gî$ï¸3G·Å¯±²M4O).¬¤¨ÎçëßÕ·²r3#ÞÊ Ì.ÓëäÔËåî0|,"òM4O).2a>DB索įL¹GL._
Rw.ÞÊÌØÏÝêÔíàêëØÉÈ_!.io£ÀºãÕÚðÑÕÚì-.i o¥¬ÃÓëäÔË峡Âv¹ñG³610·£Àǰ9G¹¥M%F»C¬
Ã(³¡±¯¯¾*¸3Ä¥@<ªÄ¯¥6¢·¿®Ä¼µ)¦§*¥3Äé´¿¶§c}138 äÕ×íc}256 ¸c}¥|ÅÄUc·ªÄ¯#¹ÈÛÞëÕÚØÏÝêÔíâêÐèå(ATP)´«² 12¸Os¤Á¸c}¿|ÅὝ ·j¬4¸yAc}v·X¥ÁÄ4¸ìio
ÀÂ?·²]£Àº¥ ªÄ¯
h HîM)ìE&ï+[=zd·1¬ÃW8·1;«¯DNA¸f`\=
Y gVî2)ìxZïL/F-zdmu´E{'´Æ`¢¯zdNKq\beQ T î)ì4ïuU=ÆN¬ÃMRIâêíá¸c
~ nî:k)ì^4ïÍØÒíéÔÌÎÓÑÜíÖ¸;RP·1¬ÃæÙéio S#¸ÓëäÔËå¹201058·)·²ªÄÃ/³¡Ã
"( ,+-.#%
Department of Molecular Biology, The Scripps Research Institute
*$!'
0/
°!{/ïÌ",!§ÐÛ¬WÆy [VÀ¿/v3pê/ßk3oÜ /,! /0-"ßk3¸¶^j/#¶ÍÓj°!{/ïÌ
#¹ /}å²¹!,.À¿"s v3Ú /,! /0/`$/
¢Ô!õ2/Ù¾å!ÍÓj"r/#Z"Ù¾å"ÁX_¸3ã&/!¶Í ÓjÀ¿Ù¾å"(3ì¿!cú/v3Ú ßm¸0$ø!îxÖÒ-0/
'¶^j¥sx±3kÞ¯¥s/ß¶´«±å3ÍÓj!w.ç'/)!cú ÍÓj"cú3Õbä/v3Ú ß #}ÃÂÇ-»¦"©¼'"ù|!
ÈÒ-0/²!DNA;SC/4LFð3Ì/Ù¾å ,%JI@Cß#
/DNA-¶ÍÓj·¶//"¶^j/#¶ÍÓj"v3Ú )!¸/Ò-0/
T"Ø+¶´«±åïÌ+P=I?SÁX_¸/±å#]k¢sx±/"
]k¢sx±3Ëuhq³¿ûì¿!x/ª"ó½'0/¶^W·¶
0¶^¢Ô"n!õ2/]k¢sx±"#ïÌv!,.x0/ïÌ3!
ßáàÊ!,.ûk"ïÌ3¸ *ïÌßv!t/vìÊ3/0
$¢xUg0ª/Ò-0/]k¢sx±"x]k¢sx±Ù¾å
"vÙ¾åüïÌý"v#¢s 3æ! X!õëx//
Å#ïÌ!,/ßv-]k¢sx±"xv!'ié/5DLR¢¡!}v
3ß/Ù¾åßJI@Cß ,%]k¢ß"oÜ0-"m¸!²
!!("¢Ô3ß3oÜ®!ñ®3 Ä"ÂÇ3ÎY/
/)& ( %
5DLRWô^#¢xs ! *ïÌv! *ÌÌÏxv3#)/
v!¸-0/ñÝ 7OGE6RÊa^/éN<R¤}"eò4LF}+þÉ"4LF}
#WÐÛ¬W#IQBRs0¨ ¿!v/# 14OCMS>ï Ì"«í\"5DLR3/N<R"4LF}#²l!]pKa d3WÐÛ¬W4OA HC+:BR"7OKEO}!¨ ¿!v//¶5DLR*Tk"
4OAHCv4OCSOÑ^3¶/üz1aýÙ¾åß"¨ ¿!v/4LF}
#4LF}º§µV!{/~x/#4LF}èf!/£!×ö¤}üN<R /#4O9ERý÷ö¿ÁX_¸/~x!â)-0/4OCMS>ïÌ A7OK8
>RXA$#&Í´-¬%g2S?W`Ð7PJr59PW/)9PI:Qt5¨2 1,3 ?=FWfi¥'30&Í´&¬%g27PJr&¸&®²%©03 Ç&;H PW&¨"c½»%2&%}1,3 ?=FW5©2"{|$;HPJW5¨2Öo1b×
&;HPJW'¦¬$UVlh52&!UV£|%/1;HPJW&¨5b2"!2
$41,3 ?=FW"&;HPJW¨5%;HPW.9PW9PI:Qt5¨2"&!
2&7PJr&yq5¯Á!2*pZ% 1,3 ?=FWÂ~^5p|f ";H PJW¨%r &7PJr5¹«Ã¾w5&pZ%FRCM2"!2
*°'1,3 ?=FW"&g%/ 03YÊ&7TGRXA^Ö7TGXTg/)U FV7TGXTg5¾w2^×% ?=FW"&g"¾w¡"&Ñ%&ÒÁ,0 32"5¯Á 2Ù×
oÙØ;HPW%/27TGXTg";HPJW¨
ÅY|&É5]cx&OMBGÀ¿3 2Õ¾w¸&À¿"$2"**
nÔ!2R9LRSX&[0¾w¡%r ¾w5Ì2"!3(Õ¡f&,
&OMBG&É5À¿2"$/1Õ¡&OMBG¾w%dË2"!2!°
'7TGXTg/)UFV7TGXTg5/1Õ¡!¾w2OMBG5 2,%¾ w_¼&OMBG&K6X?R9LRSX5©1,3 ?=FWfi¥"&µiÖ*';HPJW¨×
5%Ì5º$ 2×&Ì!'/1g&ÕOMBG'Ó03gÑa%;H PJW5¨pZ%FRCM32&%}?=FW"g$OMBG' ¢32p
Z%FRCM3K6X?OMBG5mhu0%?=FW"&g%/2Ì5¶1Æ
"%/1R9LRSX[&Õ¡¾w&k§5Z2"!2
$4S?Wr5k+7PJÎ r02 NSC<@OMBG&Ú³%7PJÎ r
&v¤ ±&7PJÎ032R9LRSX5\eK6X?E8@MU9>@DQ%/1?
=FWÂ~^"&µi5%Ì5º$ 03OMBGÖ r×5fz¬%i-"&
r&OMBG"Ä2";HPJW&¨ÈjZ*7TGXTg¡/)UFV7 TGXTg¡jZ @O<FT£|0 03OMBG!'NSC<@kÏjZ 2"41R9LRSX0Ì3&Ú³ r[%S?Wk*3 $"0-
¡jZ'NSC<@ɸ&jZ%ª2"·03Y|&É5"0$si%'¾w¡
O NH2
OH
Enz –H2O Enz NH
Enz NH
R OH Enz NH
H2O O R OH Enz NH2
Enz NH2 (a)
R O
BH B– B– BH
H
B–
BH
(b) O R' O
R' O Enz NH
BH Enz NH2
BH –H2O
IÁ+9";:,bfYQU¬Û¡:CEäã¾9¿qv¹;¸¡B¼®·;¬Å'Ì79 ELd^'¯©¾: 6(FC#:9EÒ±I¶.F7Ë$DGF
)(%&
mÙ; ;caX\<Ò±'m,5"FA;;h[iLg\kg 6<A7; ;c aX\7Â; æ;xIo$Ö;ÓÕÌ:<p,&321*6caX\Ò;t~
Ö:.Fµ»m;2@:7"#¢ºI˪,2é*;¢º6<
Ö;ÓÕ:àHF\eNjIÒ\eNj7}¨É¾:49"6Öµ»IÁ.caX\IvÐ.F èëéÖÓÕ\eNj'Ö:,5Ï6É7ÑâIÊEØ.71;×y6<Ý~¾:Ö²
'ç)9EÒ±\eNj<*;Ý~¾:ç"Ö²; :C35|u6<Ö²<t)5A ç"Ö²I¹"2:¥.F ÚIF*7'6(F7Ë$DGF*;§°:CF7Ò
caX\;±ÝsIw ;Ö:-5vE&$F*79)ÖÓÕ\eNjIE¤$F*7:CE à ;Öµ»IÁ.caX\IÆ:vÐ6(F7Ë$DGF
ÖÓÕ\eNj7,5`KkTZMUahN:C35Ü£+G2`gPhVNj:É.FcaX\
Ò\eNj7,5mÙ; ;caX\I¹"*GDIÉ,2 ;caX\I¾:¡
,2*; ;caX\<`gPhVNj;Ý~¬ÛI>9"Ö; 6<Ç ;ìxI Á,2;:,`gPhVNj;Ý~¬ÛI?Lg\kguIÖ7.Fh[iLg\kg :%"
5< μ ;ìxIÁ,Öµ»;m'ÀÓ+G2"/G;Ö;:A<Ä6!32*7
&DÖÓÕ\eNj;r<Ò±:=7J8å0/:Öµ»;m:o,27¦6(
2*; ;caX\;Ld^ßl!2E; <
³;ÞÈ;;náx:¥.Fx6!32é
ëê(a) ;«º (b) Öµ»;m,2caX\;Ò
*($"&# '!
TS[j7O]d^jI¸¡.FcaX\<ͽÖ:WR7,5r,5%)7WRÝ~;TS[jÔ
u7; :CE_PXjBÎz´Ä;~IͽÖ:{6(F</6!F,&,mÙ;O
O
O OH
COOH N
O O
OH O
O
N O O
O
O O
H
Fluorescein 35-mer peptide
Km 8 μM +
Peptide catalyst with high substrate specificity Catalytic
domain +
Binding domain for specificity
Modular assembly (a)
(b)
EMFT7(g¶!8QDUQl0RCS8QDUQl7·u4KIAD*;P>LU
&$±²¡»)@<&$f4(*Wn%"!OJQevyc(f4!/(*N FLU&$±4KIAD.Ñr1,ËÌr)O9HOPU7d &:EMF T7&4Ã&Ó¦4*Ò¦-)O9HOPU)¿h7®3¾ÌËr)?=
CT&:EMFT74±7 #KIAD ÈqÍÉ7g¶!)KIAD*NFLU&
$±²¡»(@<&$Zh?=CTºy^&)l(13OJQev7²¡»(yc4) (4&%!ÎÉÈqÎÉ)KIAD*Àz)l·u)1( l7hÁ46
%*'Àz&*'4l7£2{°)·u%4&¸4
qÍÊ?=CT&:EMFT74KIAD74)(_!KIADO9HOPU
qÎÊ:EMFT74KIAD7@<&$²¡»(OJQ7yc4
jwl)´7½Á¨k(d4*O9HOPU2)Ç·u)i¢ª·uÅ)
)¼§(%4 %l4&³b}|sh4LR9MDºy^7$:EMT
(14©©¬m~l)´7³b)sh(13d47Ä !ÏÉÈqÏÉ)7f
4&(13·u):EMT±7½Á(¹a%!ÐÉ)*^·u1,KIAD·u (14µX%)l)´)d]ev8MT7·u&4uX%)ml(i '·u1,l[)ª§(i%"!`+52)³bx(14l´)¹a7
ÀzpÆ%4¥^¢(Ç,Y¯8QBGD):EMT7«48QDUQlL9=Ql
§7¤o'[Vi¢(´'7Ä !ÑÉl)´(\³b}|)tj)x2*
CHNHQKATC AAVAKPP VSVQTKY NPLGAKL AAMDAKNSPASA DLPIPTTKLGRS
CHNHQKATCTAQAQSXXXXXX CHNHQKATCRRMRSRXXXXXX CHNHQKATCSWVLVPXXXXXX CHNHQKATCPRDRHGXXXXXX NPLGAKLAGVFWWXXXXXX NPLGAKLAMAMWGXXXXXX
CHNHQKATCRRMRSRETSVKK (rpf1368) Sequences of peptides
CXXXXXXXC XXXXXXX XXXXXXXXXXXX
Selection
Selection Libraries (first generation)
Libraries (third generation)
Sequences of peptides that bound to the diketone
CHNHQKATCTAQAQS CHNHQKATCRRMRSR CHNHQKATCSWVLVP CHNHQKATCPRDRHG NPLGAKLAGVFWW NPLGAKLAMAMWG CHNHQKATCXXXXXX AAVAKPPXXXXXX XXXXXXAAVAKPP VSVQTKYXXXXXX XXXXXXVSVQTKY NPLGAKLXXXXXX XXXXXXNPLGAKL AAMDAKNSPASAXXXXXX XXXXXXAAMDAKNSPASA DLPIPTTKLGRSXXXXXX XXXXXXDLPIPTTKLGRS
Selection Libraries (second generation)
Sequences of peptides that bound to the diketone NPLGAKLAGVFWWGQTPGG
R
O O
21-mer peptide Lys
NH
protein of interest
R O
R = Labeling compounds 21-mer peptide
Lys
protein of interest NH2
KWcs^-p*a/;AEt&Yq{I-¡¢M*
')V/=B1F*aYq-§*tT
\¬«O_U')ZltYq£-O_U')}Q*wL
(Yq*Okj_U*.B8?:-§.B8?:-Yq.B:FBY q£-O_U')}Q*w-§¯ª©\ªo|.B:FBYq£-Okj _U')N}Q*w(+ (.B:FBa%N}Q*C9 D.B:FBYq')arM&a[f,+§w').B :FBa-.B:FBYq]M*'wHna§&r
Mm(+*
\«O_U').B:FBYq£-}Q*wYqL
`& r JRbyWZ*JRbyWZ-XdPV
¨¤uZt*w§z"+*¥/;AE~'*aJRbyWZ
)(z#t-¤uG*Yq-a*Rb-SOcr.A>¦
iK&¨je]W+W Z~hG*yZ tYq-§L z#KWc-v.A>¦
iK-NZt*$
@E<6?Yqa-§
.E5K2EK-S)R*
*/;E50¤u
@E<6?Yq-gx*
tT°ª©\®ª
N HN
N O
O
N HN
N O
O O + O
weakly fluorescent highly fluorescent
HN O H
O
HN O
O OH
O +
weakly fluorescent highly fluorescent
H CO2Et O
R NHPMP H CO2Et
N H
O
R
PMP N
H CO2H
Me
anti-selective +
NH
syn-selective CO2H H CO2Et
O
R NHPMP
3 2 3 2
(2S,3S) (2S,3R)
R1 CO2Et O
R NHPMP H CO2Et
N R1
O
R2 PMP
anti-selective +
NH
syn-selective CO2H R1 CO2Et
O
R NHPMP
NH CO2H
3 2 3 2
(2S,3S) Ketones (2S,3R)
Aldehydes
NH CO2H or
\®«3.47C0 '!/;E50¤u@E<6?Yq
[9]\=82?@6[9#aD CM <e[9J@6[9#5;
CM[9#0/L Q^#T* =8<L@g'&
$%@ XO_@[90Z3W V hbSHW#+.:FH14KY EI#cN (>! A7bSY2?HGd" A7)E#U4"
-!FH4BIXO_aDP,f2?XO_@ '&$%@[9RcN`
V
1) Tanaka, F.; Fuller, R.; Shim, H.; Lerner, R. A.; Barbas, C. F., III. J. Mol. Biol. 2004, 335, 1007-1018.
2) Tanaka, F.; Fuller, R.; Barbas, C. F., III. Biochemistry 2005, 44, 7583-7592.
3) Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc. 2002, 124, 3510-3511.
4) Tanaka, F.; Fuller, R.; Asawapornmongkol, L.; Warsinke, A.; Gobuty, S.; Barbas, C. F., III. Bioconjugate Chem. 2007, 18, 1318-1324.
5) Tanaka, F.; Thayumanavan, R.; Barbas, C. F., III. J. Am. Chem. Soc. 2003, 125, 8523-8528.
6) Tanaka, F.; Thayumanavan, R.; Mase, N.; Barbas, C. F., III. Tetrahedron Lett. 2004, 45, 325-328.
7) (a) Mase, N.; Tanaka, F.; Barbas, C. F., III. Org. Lett. 2003, 5, 4369-4372. (b) Mase, N.; Tanaka, F.; Barbas, C. F., III.
Angew. Chem., Int. Ed. 2004, 43, 2420-2423. (c) Mase, N.; Thayumanavan, R.; Tanaka, F.; Barbas, C. F., III. Org. Lett.
2004, 6, 2527-2530.
8) Tanaka, F.; Mase, N.; Barbas, C. F., III. J. Am. Chem. Soc. 2004, 126, 3692-3693.
9) (a) Mitsumori, S.; Zhang, H.; Cheong, P. H.-C.; Houk, K. N.; Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc. 2006, 128, 1040-1041. (b) Zhang, H.; Mifsud, M.; Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc. 2006, 128, 9630-9631. (c) Zhang, H.; Mitsumori, S.; Utsumi, N.; Imai, M.; Garcia-Delgado, N.; Mifsud, M.; Albertshofer, K.; Cheong, P. H.-Y.; Houk, K. N.;
Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc. 2008, 130, 875-886.
10) Tanaka, F. The Chemical Record 2005, 5, 276-285.
4921
"0(
%#$#$8&$,/8'+!$67
%#$)*!$ 5
£ £ £ £ £ £ £ £ £ £ £ £ £ £ £ £ £ £
-3 .
;:
£ ´ÇBÈc&ªÑl)4ux ÇèðøßôâøÆux|Õ¶»Â²a Õ±ªÐ°Ä¬µ·«Ë º¦btÅÄ´Ó¥v°\ Çux|ÕZ¯»Â³Ñ´ÄÆÅÓ¬ÄÈ0ÆÌJÀ®ÐË»Öø½¦\
*Çs`Æ#ÀÂÈ¥Íͨ1PÅ©ÆXѯÄJ«Ëº°¥µ7 ÒÉÄJ«Ëº¦9¸>|Õ
¶»Â±ËºÄ¥4VÈ¥]=1Ç<plÏÇq¶Ò½¡{Õ=4ri¯Ï×ôöÞ¸½
¨nfK¤{ '©Õm«½[ag2z{"HƺÑի˸½¦´¿ÏÇuxÆÁ«ÂÈ¥
kN;òìÇìßêÑE5lÄ(Ã¥ ÊÄ:Õ,À«˺ ¦ _ È1Ç'M4wú°¥"H=4°ëøßÇux6Çú¦¥k-ÇvÇuxÕ|¶»Â±
˺¦
<:
£ 4#FE¥úAÆÌû]1÷4l)=48TÇ^lÇux6ÆOĸÂSm«½¦CY¥^
uÃÈ¥3=4Õ¢¸Â`§ÅÙîòâöéÚÕÐ¥¼ÒÏÕl÷/ÃmºÑ°1±²:¶
Ò«½¦¼ÒËÃ?Ç{¸¯À½´Ä°Å¯À½vÈ¥{ÌÃÀ¸ˬ4l¶Ö°ÜõÜõ«Ñ ux6ÆØóãïøÝñäÚÕ$³ÁÁÌ¥hjĨ¯W¸«´ÄÕÍÏųÒÉù©ÄJÀ«½Æ À½ ǰåòößÛóâíçøáúûêѦ[ag2z{"HÇiÇüÁÆ¥zÇeGÆÎÑe
"H¯Ï'M"HÊÇ@ÇÝ ê尪Ѧ¼ÒËÃezÃ{
fKÕº´ÄÆ+¸Â«½v È¥eëÄÌy!Æ[}'DM Õ2ºÑ´Ç{ÆoUÇIÕR² ÄÆ¥¨´Òȼ¬¾©ÄL¹½¦
È¥.ÄÅÑâöéÚÇ d.Äd.ÇÕQrÆ
}%~Å{êÑú;û¦º ÅÔ¿¥æçøªÑ«È×Úà
ĆÿēáÒßÎ.¦ĈĆĀăö{âòÿđĄû¦ãÿüáÒß@àÍóæÃ+" åĈĆĀăÿü±ö¯U}
ã¡£ÒßÃ{ÿđĄû¦ödiÔòÐáÌàÍòÛôÈáÉÚÄhìß!àâÒíÉØÈâÐáàÆÝ ÚÌÃÐóö;À}ãÍÜ÷áËìÚåG^GÚðâËÝÚÄ
!
Á {âòjö_ÔòÿđĄû¦öÃ%ÅäjöWâÈÐáâΪàÍóæÃJðóò&ÿđĄû¦ĕćāĐ µĖöjOÿđĄû¦áÒßyÔòÐáÌàÍòÄ&ÿđĄû¦öJòÚìãåÃ}ã9Odi ÌyÇðóòËÃ%ÅäÿđĄû¦öýēăÔò°5ö°5 VÉSàªÒß®Gâ<à|wÑ ÖòQoÌáðóòÌÃØóÙó"M¯UOá<àä#)'!&($Ì+¾áâòÄ[Ã+"öyÔò0&åÃ
>¤ÿđĄû¦èäÿüÏÑÉàÍóæÇäàÃmyOäFÇQoãâñJòÄ)äeá3´eã ïñÑóÚKxtzb+"ĕÃĖåÃ.¦u{OÌl¨}FÎÃ\â.¦²ãºÔò/(å âËÝÚÌÃé¿zbä+"áÇÃ"MãöLáÖÕÃ8:àRÇ]ÇÐáËðö~>¤áÒß yÇòÐáãÒÚÄ"M¯UOäsËðÃ.¦u{OäFÑÌ+¾ãâòËíÒóâÇâÃáNÇÞÞíÃêÕå îÝßëïÈáÇÈÐáà~ö¹4ÒÚÄ
Á G^ĕÊØðÎ íˏf~ãånBä VÉÿđĄû¦Ì§ÌÝßÇÚÄØÐàÃE¥ä³ĒÿđĄû¦ãÉà G^ä7xÑ÷ãAÒÕÞþđĆďöÏßíðÇÃêÕå ár×ßÃÒæðÎYÒßÃÉÚßä öqÔÃáÇÈgöñ©ÒßÇÚáÐôÃ&)(- '"+"zbä*"*,&!"öÿü²áÒß_Ôò
ÿđĄû¦ĕ,$ĖÌDdiÑóòÐáÌËÝÚĕ ĖÄdi"MåÂà ã«ÒÃ"M
HízbäpOã1åðóâËÝÚĦµcãïòdi±ä':ãºÒßÃ'7x*C7
?Xä¶`xá'~öÑÖß½ÍÃ*"*,&!"ã6,ÔòĘÞä0+k.ÊïçėÞä'(k.Ì ä¡£þùĂáâñdi"Mã=ÒßÇòÐáÃaä¼ã6,ÔòZä'(0+k.ådi㺠ÒßÇâÇÐáÃö\ðËãàÍÚ ÄÔâõÜîG
âĈĆĀăÿüöÔòÛÏàÃĈĆĀăÿü¯U}Ē _&}âÿđĄû¦diö!ã¬P$âÐáÌ ËÝÚÄ
Á*"*,&!"ãåã¡£Ñóò'(k.á0+k.Ì 6ÔòÚìÃ{âòÿđĄû¦äªãØäêêyÇòá
ĉĎµÌ ĔävàxÓòÄIÝßÃćāе
övÎJòÚìãåÃ'( äëÃ0+ äëö_Ôòÿü öØóÙóÔòLÌÆòÄä;ÀËðà Ìċú üĐąđËðćČö#ñ»ÇÚøĊċúüĐąđö.¦áÒß
¡£ÔòÐáÃdiþùĂÌċúüĐąđä %"'&/ ã 6,ÔòÐáö\ðËãÒßÇÚÚìÃ%"'&/ äė±
ĕ âðçã Ėöÿüäýø²áÒßÃØóÙ
óa·-T.ăčùđ+ .âðçã2zbøď
G )8+2/231./567'&*9(,' 8:;F$ ) @?=>
F% HAD<DI H '&*
4(,'# !"+3-0'&*4(,'BD C5 (,' E
ÊèâÑÞÇÓëÒì í· Il¶0ª¨ÄÁÆnz6 ¶ÀÃNR!9¶ª³¨ÅH½·
%' ÎêÐçÍëØÆ7è³£²¤7ÁÄÎêÐçÍëØ·%'cL> t$W: cL
qW:¸¶»¼@©Ä±¡ÂJÎêÐçÍëØÆbqeX/U¶¡±¸%' ·> t$
W:·_¶D«ÃO;4Æ<ª
%·bƧÃ},]:·î°¶(%T)·ÈäÛ)¶ QµîpÈäê0¿)³ª
±#vµ[£A§ÁÄ訲ÓêÜË·Èä Û)¸%¶)³ª±©Äµ·®Å¢ð³q Kµd'£Y¬¨² Il¶ ( ÆCT)5ª
Æzª¨Ä£¶ÀÂ)³ª±©Äâ´¢
Æi¢¾Ã¨³¶ª¨¨²¸NR·ÜëØÚëÆw3 NR:áßÕÙÓ̳ª±¥!(áßÕÙìí Æ Il¶ªÐÝÙéxqìí³ª
àÖéÔÉãëìgfÓêÜËí³sB · w3NRa\²ÃâæÔÉãëìa\íÆ ²|
¦ÁÄÃÀ¶2+ªgfÓêÜË·"^¢Á Il
·!9:Æ~«ÃoÆPmª¬·tMIl¶
(T)Æï°®¦5ª£ ·)³ª±©
Äè³£FÁ¢³µ¯ì í©Á¶!( áßÕÙ¬·¿
·Æb±!(áßÕÙ (ÎêÐçÍëØ·z
¿#v²¯¨·¨³¢Á)³ª±©Äà "T)
·¸8{²Ã£%Æb±Sv:áßÕÙÆÓê ÜËIl (·ÈäÛ)?f¶0#vµ¨³£j
&©Ä
-2.f=U²¸Il¢ÁIlE%ºÓêÜË£Óê×å¶t©Äy$ÓêÜ˪¢z²
¤µEÈäÛ·¶ % ÏÉØÆ0«Ã¨³£²¤Ä¹1(·2ÓêÜË£7Á ÄÃ#v:£ÃGÓêÜËIl·)ìæÕëÞí³Il ( (·ÈäÙ k!
9Æ},«Ã#Z:#$&% £Vg©Ä±Ãu¸t(ì#$&%í¢t(ì%í¢
¶*¤µh£Ãt(q²Ã[Æ`¢ª·9bÆr«Ã
< $ "() 76+ #'" 0237 9 8 5 0 * 3 :
&&%" 0231:
"() 4;-. "!% 14;/
-./,1:
» lO % ðñõÿÛ¾+*# (! ',#&(! +*)! ¾+*# (! ',#& ,¾ %ÚċÓÚóąùïBÅæØç¾½ ½ ,½ %ÖÁ¶0¦Ùåçûÿ«ÕÀè % Æ©Ëé¾0g¬ÚaA
ëÌÔ(¬Æ¥Íè¿ÊéßÕÙ
¨0 EÃÙåç ¾ ,¾ %ëó ąöÿÙ¤ÌÑs°'óąùïÆ
ËéÔÁÑÆ¾| V£ÚÙå çØaAÆ>æéÔÁØÅÒÑ¿ÏÊÕ¾ Ú R Y ? ë k Ì Ô 6 ' % óąùïĈĉëÍè
àÆØËéÑ¿ßξ®j' % Ù Û¾Ú(ÖØè$&-)](ÆG1
&ÌÔÁèÊÖÆHæÅÖØÒÑ¿ÊéÙµÌ Ô¾;I±SvÚ*zÙ&2ÌÔÁÑ
97x<!Û¾ %ÚJV£ë(Ù¾¶0¦Ù´êÒÔÁèAÚÀèûÿ¢Ú$&-)] (Û1̾Ïé,Ú $&¾$&¾$& ¾-)¾$&¾$&¾-) ¾-)¾$& ¾-) ¾
$&¾$&¾-) Ú](ë¾ÏéÐé)&](¾("](ÙEÍèÖÁÂ-ëäÒÔÚÉÑ¿ĈÊ ÚÚ².IÙyÛbÌÔÁÑÚÕ=Ö±SjÖÚ³Õ×ÚåÂØäçÖçÆÀÒÑÚÅÛÅæØÁ ƾãÌyÆ=ÚÏÜÙ5Ñæ¾ÄÏæÈ\âÑÖ@¿ĉÖÙãÅÈÙã¾ÊÚ %+n Û¾ãÛäÚ(
ÖÛØæÎ¾¹ÈÞÇÊÖÙ®j'Ö§ÚØÁZëw̾$ċÚWØ0FĈÖ97!Ú2>ĉÆÙ ØÒÑÚÕÀè¿
» ÊÚåÂÙÌÔ>æéÑ6' % óąùïÛ¾s°'óąùïÙ^ÞUâÔhÈ(¬
?ë/ÍèÊÖÆHæÅÖØÒÑ¿ ¾ ,¾ % ë~¯"áVBÙ^Þ¾6'óąù ïÚ/aAÛUâԺȾ«aAÛóąùïd:Ù[Ú1AëwÌÑÊÖÅæ¾0Õ¶0¦Æ ÇÔÁèÊÖÆwËéÑ¿NBQÛ¾ Úóąùï82®ÝÚ?kÚLkAëwÍØBQÕÀèÖ
ÃÔÁè¿
» óąùïÚ%3Û¾jeZëLÙkÍèÑâÚ(qDÚĊÓÕÀè¿K¢¾úĄõíąìăí äºaAØ%3«ĆóąùïÚërXÖÌÔ¾ªfnpØóąùï%3_Ú²oÆ`rËéÔ Áè¿ÏÊÕ¾ëkÍèªfnpØóąùï%3ÙÓÁÔTÌÑ¿(NCmÖÌÔÛ¾ªfnpó ąùïRY_Ö W¾ßÎrpóąùïÝ (üúôøë4Íè¿óąùï%3Ú)¾%t(
PÙÆØ?A·ëVÍèÊÖÆ[Ú¸ÖØè¿
» ßξ0ÙÆ(ÖÌÔÍè$&-)](ëGLÍèîòíąë¾ýāñôăąÚ{'þí ïĄúăć÷Ùei#uÙåç%3̾rpóąùï%3ÚÑâÚ¡)ÖÌÑ¿ĀöĂóąùïÖÌÔ¾-) ](ë"á(üúôøĈĉëM}ÙÌÑ-lOë̾%3?c:Û ¼ÖÌÔ
Óßâ'5EÓÆÊÑÄ严ăøü÷ñ¡JrÒ Ô'5ÁÒÄÑÁvÅãʹT~ÐÕ¸
¤EÕ'bn±ÐÇâÄÑæHƸy¬7Ô&æsrÑÆÏ+Ąăøü÷ñÑsr÷čĀðÔ ªÓ`r¨¼ĄăøüĉčîĎæ:ÇâѸ'5iÔ!ÁлÍʹ
¶ ^Ó¸_+æ"Û+Ąăøü÷ñďĐæSzÓÆÊÒàÖÓñĊ÷øíčûĈčõāëĈ ĎöďĐæÆÊ¹Ô1Ó¿¼ÏÕ¸¦l*Ó2)Çâ_+Ô ãÀÁÓÅãâÄÑ Á6´rÓPàÀÑÒÍʹÈÄи_+Ôd0®iæØÊÑÄä¸Ô ÎÔ_+Ô½Ì Á_áÔ_+Ó`Ø(rÓµ¼ďĐæwÆÊ¹ÈÄиÄãæÓ MÆÊÑÄä¸Ô°+ÑÒ âÄÑÁvÅãʹ
¶ ÄÔß½ÓÆÏDÊM¾ÑÕ¸BÓμϰhp#uÓßâÿùðñĈêčüÔ.ÕàãÊÝÔ Ô¸ÓßâĄăøü÷ñ¡JrÒ÷čĀð'5
ÁÒÄÑÁvÅãʹ%c¼ÄÑÓ¸÷čĀð
Ô'5ÕÐßáißÃÆ¸EÔ
Õdb~ÐÔ÷čĀðW\ÔÈãлâÀà
ÓôāûÆÊ¹ÈÄи'5QÔ-f>
ďéíč?>ĐÁ'5iÓ¾âA²ÓμÏY
ÆÊÑÄä¸-f>ÁÁâÑ'5iÁÃÒâ
!ÁàãÊďĐ¹ _+æ"ÛĄăøü÷ñÕ GĄăøüлâÊܸÄãàÔM¾÷čĀð
Ô{gÕ¸ÈãÉãÔ¦l*÷čĀðÔ{g ď ĐÑ [лâѾàãâ¹O¸îöéčÔ{
gÕ ¸Ô{gÕлâ¹'5E Õ¸9÷čĀðÓ:ÅãÊ£¢Ñ ÁèôĊ¤ªæ@IƸÄãÁ't±Ó'5 ÅãÊîöéčÔ! _+ÑW\ÇâÄÑÓßá
Çâ¹CÍϸ Ó¿¼ÏèôĊ¤ª Ñ+U±Ô¯rqÁ&Åã¸+÷čĀð
ÔRf>ÁµÙâV¸'5iÁµÃÒÍÊÔ ÐÕÒ¼ÀÑL8ÆÏ¼â¹j)¸ïĈõ+U±æ R]3rÓkÇâÄÑÐóéûæZ|Ƹ
ăČúéčèċé×Ô<©æÚϼâ¹
¶ ÔḠÁxºÔèĆč:æ¢hprÓ÷čĀðÓ:ÐÂâÄÑÕÄÔ¤Ôm æµÜϼâ¹6«¸kaG÷čĀðÔ]KÑeo45GÔ!æsrÑÆÏ¸ćýèĆč*ąĉì øċčñĉòĎĊÞ=*}§Óßâ¢hpr³Á,$Åãϼâ¹ÈÄи;Æ/åÍÊ1æä½ ÑF¼¸áçËÔÁX¥·¤þéĂĉùüÔлâ¹X¥·¤þéĂĉùüÈÔÝÔÕNƼÝÔÐÕ 9 7 8',*( !" 7%8 ).0-52461(+&
) ) :# ) -36/ $ ) ',*( !" );
Å´¨¼ÇÆÈPÆ)´ÇOa±JX·×Á¬Ö±¨xÚ¿½¢ÈŰ¿½ąR¨%&$(#
&#')!(&#&'Ã! "'(&)ÚyÍÙ»½ñÝóþêî±% ·×Á¬ÖĆ©Tv±ćwÜ øĂ5·×½ Ȩ EÂ2QÆFÆ×ֶñ²ֶðԨýõÿ¸½¬çĂò߯ !#
ÚÎ$öôéîçàÚ5¸Á¯µÉ¨' @ÆÓÕ2QÆW¦xñÝóþêî±?Ô×ÖÐÇÃ|®
½±¨1 ÆÈ¡9Æg±B¬¶Ã±°¿½©¼ÇilÆÀ¬ÁȨh#Y«֩¼¶ÂoDÚK¸
Á¨Çúìÿ$«ÖäöôéîąĆÇTvÚbAÞåëÿ¸¨ÜøðÃzºÖ¶ÃÂÚ
!#îïĄÃºÖ¶ÃƸ½©¶Ç&¨yK®çĂò߯)'ÚÎ$öôéîçàÚ5ºÖ¶ÃÆÅÖ±¨
¶×ÔǤ-$ÚyÍٻֶèÆÓÕ`pgÓ´öôéîçàGpÆÚýõÿ²Ö
¶Ã±°¿½©Ì½¨WñÝóþèÝæĄãüĂÚk¸½"0Ð~«¿½ąĆ©h#¨ñÝóþ êîÇ4Ú°ÔÊÃH<¸¨NÅWôāĄóÇÆÕyÛ¬֩
¥ ¶ÇÓÆ¨=Å /¢ÆÓÕE¤
-Ð$Æ(K²Ö
¶Ã°Ô¨¤-§çĂ òßâĂäûáĄí ÇѨ¤-§ö ôéîâĂäûáĄíÇ ñÝîāáÿøÁ ' ±k·×Á¬
Ö ©
¥ çĂòßÚ4ø½ruȨáðùC%ă[C%Ç'Ƭ¨$t°Ô@kÆÖ\ªÅruÂÌ ºÌºbo¸Á¬Ö©çĂòßÇ^~ȼǤ_[Æ3Æ .ºÖ½Ï¨¬°Æ¸Á¤_[ÚIº Ö°±¨jZÑnÊÇ@kÚ|®ÖÂßþܺ˲Å÷ÝĂíÃÅÖ¶ÃÈÌÂÐŬ©+eçĂò ßÚ¼ÇÌÌ1kĀõÿÂk²ֶÃÈ6Ŭ½Ï¨S^/ă-7/ăçĂòß7/pFaÚ£¸
ÁqpÇkÆ@¹½ą7ĆçĂòß±Ô×Á²½©çĂòßÇ{>¢ÆÙÖxÚk¬Öx7 /pFaȨ¶×ÔÇP.ÇFaÆ`}¸,ÏÁ¬Ö©'ÆÀ¬Á®É¨fÆÈ$fmA±`
p:¬½Ï¨Ç "Ç&Ç\ƨÁÇçĂò߯¼ÇÌÌk~ÅFaÆÈÅÕ?Á¬Å¬©
¸°¸¨«ÔÒÖçĂòßÚd8ÆV]ºÖÂÐŬ©$UpÆÈ¨çĂòß[ÇLÔ³Ç*²¬
Æ!#)'±.#ºÖè$ÆÅÖsg±¤¬Ó«֩¶ÇcÆÀ¬ÁȨ$öôéîÇR
ÆÓÕ¨;pÆÄ¶ÌÂM!²ְY¸Áͽ¬Ã|®Á¬Ö©Ì½¨' ÇkȨÇÃ¶Ø ÂÇkÆÔ×Á¬Ö±¨ÂÐ̾Ñ׼ŶèÑÖ˲¶ÃÐ)ª«Õ¨Ð6¸Ï Áͽ¬Ã|®Á¬Ö©
!
h v IM <V} zqi7z,ik5ummpl
F2x{zj|nzvikQW.g`NZ)#lnA[];y~n
1mzj| App{qi6^i Z } &"
3O!y}j@i7*x{es?iH=pw4etvfmqi7 LPx{erzj
h 7IMbG rptox}8 #a:\UCi N 9¡ _ #>cCi(
#.Td$CiIMRyS;ys}+'K-iDi%BX
7IMwYy} H=0/JEyuzj
1. Tahara, Y. et al., J. Control. Release, doi:10.1016/j.jconrel.2008.07.015 (2008).
2. Yokoyama, K., Nio, N., Kikuchi, Y. Appl. Microbiol. Biotechnol., 64, 447–454 (2004).
3. Kamiya, N., Tanaka, T., Suzuki, T., Takazawa, T., Takeda, S., Watanabe, K., Nagamune, T. Bioconjugate Chem., 14, 351-357 (2003).
4. Takazawa, T., Kamiya, N., Ueda, H., Nagamune T. Biotechnol. Bioeng., 86, 399-404 (2004).
5. Tanaka, T., Kamiya N., Nagamune T. FEBS Lett., 579, 2092-2096 (2005).
6. Mao, H., Hart, S. A., Schink, A., Pollok, B. A. J. Am. Chem. Soc., 126, 2670-2671 (2004).
7. Hirakawa, H., Kamiya N., Tanaka, T., Nagamune T. Protein Eng. Des. Sel., 20, 453-459 (2007).
8. 53p.21-26 (2005).
9. Kamiya, N., Doi, S., Tominaga, J., Ichinose, H., Goto, M. Biomacromolecules, 6, 35-38 (2005).
10. Y. Tanaka, Y. Tsuruda, M. Nishi, N. Kamiya, M. Goto. Org. Biomol. Chem., 5, 1764-1770 (2007).
11. Fontana, A., Spolaore, B., Mero, A., Veronese, F. M. Adv. Drug. Deliv. Rev., 60, 13-28 (2008).
12. Duckworth, B. P., Chen, Y., Wollack, J. W., Sham, Y., Mueller, J. D., Taton, T. A., Distefano, M. D. Angew. Chem. Int.
Ed., 46, 8819-8822 (2007).
13. Tominaga, J., Kemori, Y., Tanaka, Y., Maruyama, T., Kamiya, N., Goto, M. Chem. Commun., 401-403 (2007).
14. Hu, B.-H., Messersmith, P. B. J. Am. Chem. Soc., 125, 14298-14299 (2003).
15. Gronemeyer, T., Godin, G., Johnsson, K. Curr. Opin. Biotechnol., 16, 453-458 (2005); O'Hare, H. M., Johnsson, K., Gautier, A. Curr. Opin. Struct. Biol., 17, 488-494 (2007).
16. Lin, C.-W., Ting, A. Y., J. Am. Chem. Soc., 128, 4542-4543 (2006).
º
º
v7º N`º (ÀÊÃëº ÝàÛê)
+³:+/+/´k/w{º me{/4Lº ( }39 [email protected]
ÈÙ;Úm/wČüďÞÙ#\ì¸Å¼B¢Êß̽j!zÚ¼+³:+/+/´Ù
¬µMIÙÕ¼ąč®"-E ÙìtHÊwìÒÔÀß̽Ì×ëѼE ÙE
Ø~¾Ùõăîóüď.ìZ ÌèÐâÙP_¡ìxʼ~¾Ù·,dÙDõ ăîóüď.ìEØ5ÌèÖÀÁàÕ̽
º dpÚ9ÖÀÁ°À9SìÃÇÔ¼d)rìʼ«ìç¦ÌÈÖØåÒÔ¼*ÆÙ/
@ì·8ØiÆ-Ìè®ÙåÁ×m \.ìh?ÊÔÅÔÀß̽ÏÙÐâ¼o!Ø
®ìʼßÐUáåÁØÏÙ\ìK)ÌèÈÖÚ2QÕÚ¿çßÎí½ßм,d®¿èÀÚ
-E ÙåÁØE ì¥&ÖÊÔnÌèØ²ëæÍ¼,dØÚ×À$¤frAäOÊÀ\ìãѼU á@ì¹iÃÓ «GsØ-Ìèm \.ìÂåÜDÌèÈÖÚT\/Ùà
׿Íme/ØÖÒÔãRt[ÙÓÕ̽ڮ\ÙK)ÂåÜ®\ÙÖÀÁ
cÃæ¡Nì3%ÉÎÔ¸Åß̽
Enhancing Activity and Controlling Stereoselectivity in a Designed PLP-Dependent Aldolase M. D. Toscano, M. M. Müller, and D. Hilvert, Angew. Chem.
Int. Ed., 46, 4468-4470 (2007).
º Hilvert æ Ú Geobacillus stearothermophilus o W Ù PLP-dependent alanine racemaseÙ-^$Õ¿è265qt Ù Tyr ^ $ ì Ala ^ $ Ø J Ì è È Ö Ù à Ø å Ò Ô ¼ racemase Ãæ aldolase ÞÙ\K)ØDÊÔÀßÌ( 1a)½ÈÙfrs)r5Øåç¼$¤(2R,3S)--ăðā ċúĊĎØ©ÌèaA±ìmàÌÈÖØåÒÔ¼V WÙĉúĆďûaAÚ103b6ʼ$¤ÙĄĎùïċÿĂ ĀÖôĊöĎÞÙ§ïċĀďċ@Ú 105¨ÉéèÈÖÄ yÉéßÊÐ( 1b, 2)½ßм=æÚ265qtÙTyr^$
ìAla^$Ùà×æÍ¼Ser, Val, Glu, Arg, Lys^$ØJ ÌèÈÖØåÒÔÉæØR©ìÒÔÀß̽ÏÙX¼ Tyr265Lys)r ÚTyr265AlaØ3Ê9ÙkcatìyÊßÊ Ð½ÈéÚLys^$Øåç$¤ÙuAÄ'+ʼ ïćĎÙ]¶Øåç$¤ÙĄĎûĎlÖÙòýñĎ-»u
nÙ<D¿èÀÚ¼ª|gCÕmË裶ì01ÌèÈÖÄÕ¿èÖyÊÔÀßÌ( 1c)½ R>ؼ(2R,3S)-, (2R,3R)-ăðāċúĊĎìnÀ÷ïøþČñ«GAÙYìÒÔÀß̽Tyr265Ala
1 G. stearothermophilus alanine racemase)r ÙaAĈÿċ a) ¯m" b) Tyr265Ala) r Ö(2R,3S)--phenylserine-PLP aldimine c) Tyr265Lys)r Ö(2R,3S)--phenylserine- PLP aldimine d) Met134Phe/Tyr265Lysº /Ile352Trp ) r Ö(2R,3R)--phenylserine-PLP
aldimine ¡NåçF
!Q «[kcat/Km(2R,3S)]/[kcat/Km(2R,3R)] = 9.2¸V®¥-²«ªz62¸ut´p¯¸
g¢¤®¨·¡Met134Phe©´¦©±¢¤TOC+¸!7Ile352Trp¦±³)º ØÒE©^7´¦©±¢¤(2R,3R)-Õ¼ÐÜÉÛߪ -ÓÏÞÀÆÜ¦m$¦¤k¨¸´i~[ªÛß
ª[%¸G[\,3s©/®(1d)ª
\ @ Met134Phe/Tyr265Lys/Ile352Trp ! Q « [kcat/Km(2R,3S)]/[kcat/Km(2R,3R)] = 0.6 ¦z62ª8l² µ®>r9ª°¶¦¶«H2{ªE©!
Q¸(´ ¥racemase²aldolase¦Da¸8!
´¦¥²©E©!Q¸(´¦uºÜÏàÜ 1ªÇºÈÌÝ¿z62°/¥´¦¦¶¥
The Putative Diels-Alderase Macrophomate Synthase is an Efficient Aldolase J. M. Serafimov, D. Gillingham, S. Kuster, and D. Hilvert
J. Am. Chem. Soc., 130, 7798-7799 (2008).
ËÙÂŪRfMacrophoma commelinaeP?ª
Macrophomate synthase (MPS) «3©V2-ÔÞß(1)²
×ÂÞÕ¾Øß(2)ªj¨!71¸m$´¦·
¢¤®ªm$1«F©´¦¥®
1) cJ1©±´¿ÀÅÞ}²½ÒÚàΪN3
ªF« Mg2+0¥2) ½ÒÚàΦ 2-ÔÞß(1)¦ª 2 ªJ[-J[\,313) cJ-cG1©±´×
ÂÞÕ¾Øß(2)ª,3¥ªJ[-J[\,3F
«#S¨Diels-Alder1©±³yg´¦_²µ¤®
¨²QM/MMnYª\@3©V2F×
»ÃÜ-ºÜÏàÜx]1DBª:[4+2]ÖÛML1±
³½ÑÜÁàS©=¥´¦Vµ¤®²©
MPS«2-dehydro-3-deoxygalactarate (DGG) aldolase¦ºØÒ|±¬H2{ªBw°T2
®§¡²°ÄÕ¹ÂÊত Mg2+¸0¦¤´¦²>r9¥Hilvert ²«ºÜÏàÜ&
¦¤WªºÜÍÓϸOMPSªaldolase¦¤ªa2¸Ao¤®(4)ª\@b`
;e;±¬j[MºÜÍÓϸO ¿ÀÅÞ}¦ªºÜÏàÜ1¸m$´¦V
µ®(h 1)²©MPS m$´ 7a ªuºÜÏàÜ1« m$1©'105ªv*
v¸V¦Vµ¤®>r9ªdI¦¶«~[¸8!´¦¨MPS ª>?°£
m$DB¸<"©N¤´¦¶¥ .«N3KªX z6ªq¥<.©
MPS ºÜÏàÜ1¸m$¦©±³2-ÔÞß(1)²×ÂÞÕ¾Øß(2)ª!71ªm$DB
©U¸4¤®
2 uºÜÏàÜ1m$DB r9±³ {5Z
3 MPSm$´2-ÔÞß(1)²×Â
ÞÕ¾Øß(2)ª!7DB
Biomimetic Catalysis of intermodular Aminoacyl Transfer
K. M. Wilcoxen, L. J. Leman, D. A. Weinberger, Z.-Z. Huang, and M. R. Ghadiri, J. Am. Chem. Soc., 129, 748-749 (2007).
u ®¬¨ª/KHct<(.~µ¥¶º¸p
¡²«¡¤¸eP,yr·°§º³®¬¨ª.lT
(NRPS)±·®¬¨ªK.8NU(.,
zyNRPS cj1D-ycGy U(.|I#) 2}D-k(ª´¢¹)
>.| zGhadiriNRPS28N
,Bq{¡²«¡¤¸cD-k% µ
¥¶º¸p¡²«¡¤¸ePBq @^! a_
zJN¡¤¸eP, i. y*y lT^!n\^!"{g3; L
| z8b5XE|yg3; a_ 26Acoiled-coil®¬¨ª "Lyr7UN¡²«¡¤¸$ g3| ( 6a)z 5aO }'Zcoiled-coil¯µo4D-kyD-k7U
c ,% CysA~¡¤¸${LysA>.yX1,X2k
Ym^!N^!A % ka_| zyRW
Type-w~Type-xD-k a_yCf=`Z| (5b)zType-vD-k L|y
cCbz-protected N-acetylcysteamine glycyl thioester F yCysAc,
% yg3; Lys A·©£¦p¡²«¡¤¸eP,dyU(.d
z¡²«¡¤¸eP,y5400 (kcat/kuncat)hOzType-w~ Type- x L|?U;+| z
[» MPS ^! ¡¸ªº¸,
cIM- b5k0S4
4 MPS89^!,~¡¸ªº
¸, b5k0S4
¼ a)(&) herical wheel diagram () XVU 6]:b) 3QsD-ka_ b5k 0S4
E é ¸¨B Łïîé ēđøł
z@D@Dãuç7#b¥D ª¥é ĸĮġĤļĥıķLpé (<Φ3R [email protected]
øčSĎê0%D ªĽīŀďčøčėïċ8«ĝîĂăôê\ėęñ£ü÷Ēþë5ê¤
Ďz@Duç7#b¥D ª¥čyQqkčùgMčêÀÑNDčĉĕČdČ
ĝVĈĂBÍÐêČáþĚ ªČmĜąĈñęĒþëdčuÆd)ČKþĚè îÇ1`ĿÛe`č#~ĝvĘòČüêBÍÐTča:9Č9ćîĂdčwċĚ»`č .êFG`čZêíĚîĎ»o=¬ĝgüĈ ªĝÁąĈñęĒþëdófĆêîĜĖĚB ÍЮBĊüĈčí̧č»`ĊèSČ´úěĂd)ÍÐ~êĒĂêdČâĘÿÀÑ čÅċĒĉčOēċ»ħĩĭķĝ6àÅĚSê0ďčrč^ĝfĂûĚĝZĒĀĞëé é é
AÀÑófĆ»ĸĤİĪķĝÈþĚøĊĉêāěĘĝÕČ]ýĈ üêúĘČĎêo¾ĝ$
ðĂ»`NÀÑĝ¼5ČnĚêāčėïċ?Ď>õč ªºófĄ³öĈîĚĕčăĊ_îĒþë 3Ďê¼ČC5þĚÀÑĝĆčÝ2ĊüĈjðêÜBNDc ĝîĈąĂęµ÷
ĂęNċĠĽľĨĝ$ðĚøĊĉ#ÃúěĂ»`NÀÑČĆîĈčÏtĝ 2 :êĒĂêĦľIJĹ ŀīĉËÊüĂNß®ČĆîĈčÏtĝŃ:ù¯úĀĈîĂăôĒþë
Design of Protein Function Leaps by Directed Domain Interface Evolution
J. Huang, A. Koide, K. Makabe, and S. Koide, Proc. Natl. Acad. Sci. USA, 105, 6578-6583 (2008).
AÀÑč>õĎê±¶%úěĂÄsčįĸĢ ľČėĚ&-ČėąĈ»ĝüĈñęêĒ Ăêāč`ÝĎįĸĢľlÉåČ·üĈî Ěó>õíęĒþëÄsčįĸĢľóáþĚøĊČ ėąĈ@ôċlÉåčZĊ*Jċ`Ýč
~Ö![ó+»ĊċęêėęèSċBÍÐĝH
üĈîĚĊ¹ðĘěĒþëyÏtĉĎêāčėïċÀ
ÑįĸĢľ-<č&-ċBÍÐĝNČ
#ęüê'įĸĢľėęĕÙòČěĂ»Z
ĝHüĂó:/úěĈîĒþë41Č¢üĂ»`NÀÑ “affinity clamp” ĎêĶĵĬįČ KüĈUîÇ1`ĝfąĂ primary įĸĢľ(Erbin-PDZ)ĊÇ1`ĝõfĂċî enhancer įĸĢľ(FN3)ĝ
ײúĀĂNÀÑĉþëFN3ÂåČC5þĚŅĆčļŀĵČ=ĝ$ðĚøĊĉ109¦SčĺĢĴĺĻ ŀĝ~üêijğŀĨĮġĩĵĽĢ ČėąĈĶĵĬį²,ÝÂåčxÚ%ĝÁîĒüĂëx°ČZĘ
ěĂ affinity clamp ePDZ-b2 ĎêErbin-PDZ įĸĢľ'ĊÒþĚĊÇ1`ó 500 ê`ó
2000Ċîï@Pċ»`č.ĝØbüĈîĒþëÏtĉĎêńĆčįĸĢľČėęBĝi ēÓĔøĊĉlÉåčå©ó;üêāč²|êģľīļIJŀIČėĚÇ1`č.Ċêėę*Jċ BÍÐó+»ČċąĂøĊóÔĐĘěĈîĒüĂëytČĎêv¡ČĎ¢úěĈñęĒĀĞĉüĂóê įĸĢľÂåÞčbČï1~Öč=%êíĚîĎÄ,Wb"YĉčFG`č=%¬óÇ1
`Ŀ`Č@ôõXæüĈîĚ+»`ĕ¹ðĘěĒþë
ĒĂêøč affinity clamp č«þĐôčĆČê{Ŀ}Ì¿ĊüĈč`óh÷ĘěĒþë 3ZĘěĂaffinity clampĎĶĵĬįČKüĈsnMčÈäGsĝ¢üê§ìč%D ĉ½
uÎÝÜÉ´ÛĂõæćĉôąMÞ¼ÑÌÏI@ÞVÂÛ6ËÀÉ¿ÜÉ´Ó±R
Êаalkaline phosphataseÞ)ÀÆâäëîĈúćðñàĈçp^×Pull-downpËÀÉÏ
VpH°ÓÆl9:HÍÌÏÖÇÉ·Ú°´ÃÜÖ{ÍJÞÕÉ´Ó±primary óāáĈË
enhancer óāáĈÏÔ)ÝÄÞ3¶Û½Ëʰr8uKhÞÛ½ËÍ»°4aÍbuÎ;GÀÉ
affinity clampÞ!ʺÛË´µ½ÏTÆÍt>8ÏKhа[#8ÞÐÁÕ4»ÏªÊÏGp
¹WD¿ÜÓ±
Novel Genetically Encoded Biosensors Using Firefly Luciferase
F. Fan, B. F. Binkowski, B. L. Butler, P. F. Stecha, M. K. Lewis, and K. V. Wood, ACS Chem. Biol., 3, 346-351 (2008).
eаs0ąéùãĄĈÏ©#&GÞ5ÂÛ¨ą éùãăĉíÞfËÀÆsÏÞ¾ ´ÆÀÓ±
½Ï#8sаÊdÂÛ_ÕÉI@ϯ´^
hËÀɰ½ÜÓÊÎATPϯI@:«×°Ćÿĉîĉ¥6 ËÀÉÖ?»p´ÙÜɺÓÀƱYRÊа½Ïąéùãă ĉíÏÜÆnHÞo¸ÀɰÏ4aÍbu6Î;
GʺÛgpHϯ´öáåìĈèĉÏ!ÞvOÀ°3 ÈÏ qÍÛĂòąÞP+ÀÉ´Ó±
ąéùãăĉíÐ 2 ÈÏóāáĈ¸Ù`J¿Ü°ÅÏóāáĈ
*2ÐøĈê¦ÞÀÉ¢ÀÆ\ÏØµÍ`¡Þ'Ç É ´ Ó Â ± 0 - Ê Ð Open ` ¡ ° 0 7 - Ê Ð
Closed`¡Ï2ÈÏqÍÛ`¡Þ'۽˹(ʱYZ°
ČX~°CX~ËÀÉ7-ÀÉ´Û/ΰ¥6>8uKh Þp´É°bu6Î;ÀÉnquÎGÂÛþûïó§°
³Û´ÐóāáĈÞ<À°ąéùãăĉíϨiHÞObË ÀÆs.öáåìĈèĉÞ!۽˹ʺÓÀƱ
,2ĊċÎzÀÆĂòąÐ°ûćñßĉí^pöáåìĈ
èĉʱ»z¿ÜÆYZÏąéùãăĉíX~¦Îûćñßĉí§Þ<ÀÉ·»Ë°;Ë ÍÛûćñßĉí7-ÊÐ<§¹S¿Ü°ªo.Î ´¨iHÞzÀÓ±À¸À°buûć ñßĉí-ÊаóāáĈ¬¹¢¿ÜÉ´ÛÆÕΤ"¹L ¿ÜÉ Closed `¡Þ'۽˹ʺ ðsB@ÐQ%Ï Îj=ÀÓ±7 }ÏûćñßĉíÏ´ÃÜÏ1)Ö$Í^I@Þ E۽˹ʺÓÀƱ
,2ĊċаąéùãăĉíX~Ï]cÞtóāáĈ¬wpÎØÇÉ FÂÛËÍÇÉ´Ó
±FRB Ë FKBP12Ðă÷ĀáéĈË´µ#8m7-Êüñć«ÞCJÂ۽˹xÙÜÉ·Ú°
½ÜÞpÀÉă÷ĀáéĈGHÏöáåìĈèĉ¹`¿ÜÉ´Ó±ă÷ĀáéĈ-ÊаFRB
Ë FKBP12 ¬ÏwpÐCJ¿ÜðB´sÞµ¨iH¹N¿ÜÓ±U°bu67-
ÊаFRBËFKBP12¬Ïwp¹ă÷ĀáéĈÎØÚ£¿ÜÛ½ËÊąéùãăĉíÏ]c¹½
Ú°sB@¹À»j=ÀÓ±®Ćýą°ĆýąÏ´ÃÜÖă÷ĀáéĈk@7uÍs B@Ï3#¹y¿Ü°ÑÒ*|@Ï^I@ÞzÀÓÀƱbu6ÎØÚt¬wp¹n quÎ F¿ÜÛØµÍ}²ÏÞGpÂÛ½Ëʰ¿ÙÎ4aÍ^aA¹`¿ÜÛ½ËËWD¿ÜÓ
ÓÅ
ÑìàÄ, 2ģĤàãÄòĠĀćĝĆùßIgdñTÙ×ęĈĞÌÑïÛÇçÓÅĞþĒõĜĢăâĐ ġÿ³ «àÑï×ĊĘôġàf9Ì$ÓîÝĊĘôġâd¬Ì4ÒÄÖâd¬4 âN0ñµpMþúċĞå4UÓîÝÇÈ@7ßgñTÙ×òĠĀćĝĆù.ĂġüĢÜÓÅ]W ÜãÄx3ñL>à"YÒÄÆîCâ!ßOCÜ cAMP âaàQÒ×>ÂÌÑïÛ ÇçÒ×Å
f9ñÙÛ¨âd¬4ñIÓîÝÇÈÏïìâĈýôġãĨâgĘöČāėâ
¡sËìé¿Aà&qÎÄòôĈóòhÜ5eßa9ÌíÕî#Mñ*ÒÛÇçÓÅ GÄÑìà5eßgM9â~1Ì\FÜÍçÓÅ
Kemp Elimination Catalysts by Computational Enzyme Design
D. Röthlisberger, O. Khersonsky, A. M. Wollacott, L. Jiang, J. DeChancie, J. Betker, J. L. Gallaher, E. A.
Althoff, A. Zanghellini, O. Dym, S. Albeck, K. N. Houk, D. S. Tawfik and D. Baker, Nature, 453, 190-195 (2008).
[GàÐÓîâãÄûġđĚĢĄàëî?µâ¥¤àºÓî§WÜÓÅt|ËìHìïîµ
Ì£8Óî"KãÄy(ñVÉîy"Kà»ìïÛÇçÓÅ6tàã:-ÒßÇÎXÒÇ?
µñíÓÏÝÜÄ"KğďĢĉĝĢÌBÌíÄÁ)zbâæËÄ;Ä zbßÞB߸Üâ K{Ì\FÑïçÓÅ
]WÜÄ"KęĈĞÝÒÛ>½àÙ×â ãÄ, 3 àÒ×ÄKemp ¾"KÝÇȹx
"KÜÓÅKemp¾"KâöøÝßî"Kl
¼ãÄ2/àëîrËìâēĠĉġ"
KÜÆîÏÝÌìïÛÇçÓÅçÔÄèàÄ µâĈýôġãpMJÝßî2/Ë
ìn=ÒÛÇçÒ×Å2/àãÄòĀďĜøġ¶k/ç×ãúĞĄĖġ¶k/âöĞĕ÷þĞ/ÄÆî ÇãÄcÑï×ĐĀąÿġk/ÌÝÒÛ²äïçÒ×ÅÇÛÄ"Kâ± uPñ<=ÓîëÈß pM³ âòĖč¶´Ì¥¤Ñï×GÄÖïìâpM³ ñ<=àwÓîÏÝÌ#ßÃ`ÝÒÛ TIMĎğĞ̲SÑïçÒ×Å
ÏâëÈàÒÛ17Àâ}ßÙ×Ã`ñéÚ59âµĈýôġâËìÄ>½àµpMñÒ×8
ÀâµñíÓÏÝàQÒÛÇçÓÅÖâÈØâÚÄKE07 ÝÇȵàºÒÛãÄZd¬¢
^àëÙÛ>½âd¬ñn=ÒçÒ×ÅûġđĚĢĄÜQÒ×ęĈĞd¬Ý>½âd¬Ýñ mªÒ×ÝÏðÄpM³ âd¬ã¿AàëÎÒÛÇçÒ×ÅÑìàÄEìã=%®Ý'äïî¦Â
ğĔĞÜâòĖč¶´â[°ñÈÏÝÜÄ£8vñ 200 é%ÑÕîÏÝàQÒÛÇç ÓÅ
GÄÑìàĨÃ`â9¯Ä_©Mâ+9ñûġđĚĢĄÜâ¤àRÎ"YÓîÏÝÌ ÜÍïäÄëí>½âd¬à«ÇDÜþĖĚğĢþěġÌ#ÝßíÄgñvÎáÉ×i
ß9¥¤Ì\FÜÍçÓÅûġđĚĢĄàëî¤RoÝ>ÂRoñRÎ$ÑÕ×ÏâëÈߨ
¥¤ãĨ?;àÊÇÛé· ßjÝßîâÜãßÇÜÒêÈËÅ
M :Ėèàï ÓìÐÌė
?B4646¸*ºy0@6À y0@6;WÀ 2¨2C [email protected]
ÎâDãªY âjó¾Ë§áÄïÊÞÆÏÑÅçÔ ã?B46âk8áÈÅ Ü3âÝÄð-1,3-ûĐøēóc³âùčďõĕá{ÅðÎÞóSÒØáJÒÜÈïç ÔÂõēăāēÿc³ësiRNAÊc³ÞÒÜÐñÜÅçÔÊÁ~pK{óÔCpG DNAÞ (äñð1^µâ÷ďýDNAáoÒÜÁ -1,3-ûĐøēóDDS_ZÞÒÜ{ÅÁ iÝÄðP!U
áÎâc³óaá°ÔðOóèÒØÅÞÇÜÅçÔ ÎâCpG DNAÞÅÆ%ã
»ċăĐ CG þĆúđ÷ăąâ²Êeuâ~ópKÔðÎÞá|`ÒÜÅçÔ ^ÝãÁ ùčďõĕÞÒÜ{Ôð-1,3-ûĐøēâ"9(Dectin-1)á·ÒÜ/ÞÁ c³ÞÒÜâCpG DNA á·ÒÜ/Á ÐîáCpG DNAâ"9(TLR9)á·ÒÜ/óÖñ×ñÏ ÐÕܾËçÔÂ
Differential High-Affinity Interaction of Dectin-1 with Natural or Synthetic Glucans is Dependent upon Primary Structure and is Influenced by Polymer Chain Length and Side-Chain Branching E. L. Adams, P. J. Rice, B. Graves, H. E. Ensley, H. Yu, G. D. Brown, S. Gordon, M. A. Monteiro, E.
Papp-Szabo, D. W. Lowman, T. D. Power, M. F. Wempe, and D. L. Williams, J. Pharmacol. Exp. Ther., 325, 115-123 (2008).
2001Cânature ¤ÝGordon zîãĊöÿĔĊúĒĈôĕþhb(RAW264.7)á-1,3-ûĐøēâ
đāĉĂĕÞÒÜ Dectin-1 ÊxÒÜÅðÞ/&ÒçÒØÂÎâÊÞàÚÜÁ¥«±ë¹K
âv7ÁçØĂēćúâ}KâTÁ~pKáÈÍð Dectin-1 âGáÛÅÜpàÊQÒ
¯éîñÜÅçÔÂ^ªYÝãÁ-1,3-ûĐøēâµ¶ëµÊ Dectin-1 å⥫áßâíÆàF½ó ÇðÉó\îÉáÒÜÅçÔÂ
À 7 l-ÉîàðµwâûĐøēó{LÒÁÇÜ 8Á9Á 10 l-âûĐøēÁÐîáã 7Á8Á9 l-âûĐøēá 1 ÛâûĐüĕÿµóRÛ¦<â$MóÅçÒØÂ
-1,3-ûĐøē¶µâ$Mãx+oÐñð´â1ÛÝÁ
±4â. ¢zîê£èîñÜÈïçÔ #µâ
Dectin-1(ĊöÿĔVÇ,)åâ$ã ¼ĉĎĀČē
nÝ©æîñÁµsD IC50ÞÒÜm¬ÐñÜÅçÔÂ
µwâûĐøēâIC50ã7l-â >1 mMÉî10l-â
0.7 mMåÁ>,âûĐøēÝã7l-â0.13 mMÉî
9 l-â 29 μM åÞÁßÙîêµXÊ1ÔðáÛñ IC50 ãr=ÒÁÔàòÙ$Ê1ÒçÔµâ]t
óm¬ÔðÞÁ'qÅÎÞáÁ7l-âûĐøēÝã1ÛâµâáíïIC50Ê0.1ár=ÒÁ
çØ9l-Ýã2.6 mMÉî29 μMåÞ0.01DáçÝr=ÒÜÈïÁ1ÛâûĐüĕÿµâÊ
Dectin-1å⥫óféÜ4ËÌ¿éðÎÞóÒÜÅçÔ )1ãÁµûĐøē(10l-)Þ>ûĐ
øē(9l-+µ1l-)â5ČĄĐó¡ÒØêâÝÔÂÎÎÝÁ6l-âûĐüĕÿÊ1Ăĕēâ[
óEMÔðÎÞóÒØIáÁµÊÄðÎÞÝČĐÊr=ÒÜÈïÁÖâazÓØ[g®âAÊ
Dectin-1 å⥫áF½óÇðÞHîãUdÒÜÅçÔ NÃâûĐĕĉÝãÁ56nó{Å
)1À µÊÇðµg®åâF½
áāęĂĞƸç2*Ð-1,3-āęÿĝç 3 µXç¸ç³?æÍóBÀ÷ªêȸРÙóãX&(çmçy.Ð/öòÈXçĒċĊÐÒåóÕã÷×áËëÙÉç³?ã§
ãç ¼èE¤YÖôóêÑ©ÂãÍñôëÙÉ
Properties Regulating the Nature of the Plasmacytoid Dendritic Cell Response to Toll-Like Receptor 9 Activation
C. Guiducci, G. Ott, J. H. Chan, E. Damon, C. Calacsan, T. Matray, K. D. Lee, R. L. Coffman, and F. J.
Barrat, J. Exp. Med., 203, 1999-2008 (2006).
CpG DNAç¢è1984=çBCGçDNA~æ@
åúĝĉĞēüěĝ¨7ÐÊóãËÌHn Izñ ç,%æ²òëÙÉÛçEÈ1992=æDNAçCGąĐ ĀĚþĊĎætÐÊóÕã÷YñÏæ×ë×ÝÉ
1995=æèÈKriegzñÐ0}^çDNAæB
çrLÐÊòÈÖñæCGç¿ĖĊęÐrLæJ ÁâÊóÕã÷ÑkíëÙÉÕç CG ³÷$ì"Mþ
Ęăa´(CpG DNA)Ð#gçrL÷ÙÕãÏñÈ
x*ÈCpG DNA ÷|ËÝoïĜĀĊĝpç
ºæqнëßáËëÙÉ
] « V â è È A ® g h w (PDC)æ Î Ó ó
CpG DNAç|æ¼×áÖôáËëÙÉ PDCè
âeíá8åËâÙÐOûúęĆKæÎ
ËᵡåC÷PßáËëÙÉPDC÷rLÙóCpG DNAèÈÅcÄÈ ³È iç;æðòAÈ BÈCãËÌ3àç+æ0ÖôëÙÉA+èIFN-ç{ÈB+èhwçMvÈC+è AãBç i(>èÐòëÙÐ)÷RßáËëÙÉÕôëâÈrLç;Ðæ}^ÙóÏèYÞßÝçâ ÙÐÈDñèCpG DNAçRàÆjf¯æÛç¬÷¤Ò·ÐÊóã« ÓáËëÙÉ3èÈA+èBÈC +ãèåòȳ\æþĘă G³÷J¡ãÙóÝíÈGç 4 ¶AM÷×Ý1»"÷zØ ëÙÉÛÕâÈÆjf¯ç±ËÐç9*NæäçðÌåBÀ÷ÍóÏ÷È[ãE[ýĝĎĈĞ ĕç`ã×áÈOčėĝĆēüĘĝĚćĔĉĞOãOLamp-1 O÷|ËáÃG¹â£5×áËëÙÉ
_èÈF^ýĝĎĈĞĕâ;èåËîçãÖôáÑÝçâÙÐÈA +âÊôé[ýĝĎĈĞĕÈB + âÊôéE[ýĝĎĈĞĕÈC +èWâÛôÜô§ÖôóãËÌîçâ×Ý() 2)ÉàëòÈÕç"
çZuЧ-Nç;ÈÖñæèrLç;÷zØÖÚóãËÌÕãâÙÉÕçåbQã×áÈ\³æÈ G4¶÷AMå7-ČùĄG÷RàA+ÐB+gæÈ UçB+÷Ràďđ1ÐA+gæÈ ëÝpH KLç®(E[ýĝĎĈĞĕâT!)æ6×Ý C+ÐB+gæÈÛôÜô9*N
÷/ÍÈÖñærL÷×ÝÕãÐSÔñôëÙÉÕçðÌæ1çÆjf¯Ð 4æÍóBÀ÷d¥
ÙóÕãè¦×¾ËÕãÏîôëÚøÐÈ¿<æ'sÒEç°:ÐlæåóãÕõâÙÉ
)2ÇCpG DNAçrLif
Ligand-Induced Conformational Changes Allosterically Activate Toll- Like Receptor 9
E. Latz, A. Verma, A. Visintin, M. Gong, C. M. Sirois, D. C. G. Klein, B. G. Monks, C. J. McKnight, M. S.
Lamphier, W. P. Duprex, T. Espevik, and D. T. Golenbock, Nat. Immunol., 8, 772-779 (2007).
o CpG DNA"rToll8"9 (TLR9)p2000&#T nE C GY{|
q)p:MTLR9<,]${¦ª ¥pF+O(Th1)k| [1 { x~wpTLR9-CpG DNAj\_97k| ¨ª|q
o 5^/pF<,J~CpG ODN¬¤«ªgrGpC ODN(CpGcg)
w TLR9-Fc(IgG Fc 0AQ.tV)NZ,-zwJ{~q|v|wp
TLR97d, CpGg=2p~zw
U,(CD);1v{|( 3a %)q
pTLR9<,CpGgRC}7 dwhXrzwv~q8R6p
TLR9-Fci N®C4LjalwpCpG g
IS~zv* s~( 3a )qzz
pFRETB`D|m®"jal>
!x FLIM-FRET wfD{ s~q3PHp
TLR9ERi| -{ upCpG ODN ey¬¥¡©K|pCpG g\_)7d
w MyD88(£§¢) H ¥eW
{(b s~( 3b)qBpCpG ODNe )pTLR9 w ERv¬¥¡©K~97@
?w' sz~q 3oTLR97d
30&!/
2+( -1 '*( $%
6 5
x|½'OR̨´íåÙòè(~÷-4|)¾¤êÜî½'lkq¼d§ÇÊ·§É¥
Á´¤b ¼3±É P«§´Ã¼¤ÞìÛÓÜíáíò½ÑëíÏÅu!»º½ñcQÀ
½Ad¼Äd¯ÊÉ¥®Êǽkq½*¾¤LªÇLgßàéòÝîÕÐ×½íåÙòèÌ3¼°·
©È¤K¼ÆÉÕÐ×)Å ¼ÆÉ^H_s½ÏðÕðãî8&½Z0«ËÊ·
§É¥9¤x|¹n;½LæÐÒïéòÝîÖÔòî½6+íåÙòè¼ÆÉêÜî½kq«iÍ
¸¦É[1]¥x|¹ÖÔòî½6+íåÙò辤zFñRñÕÐ׼˴ÈaDh»x|êÜîrÌ J±É¥Á´³½+¬¯ªÇ¤/?¼ÆÈ ½IɧÌíÏîÚÐè¸Z0±É®¹«
}¸¦É¥"¤6+íåÙò轩ƿ?2½1¢GV¼¶§·°¤1½kqÌ y°´§¥
%öø6+íåÙòè½S<%
7 5 . 7 4 6 5 ) , " #
~½ª´ÁÈÌU¹Y¯²É¹¤~-«fh¼°çØîÅíåÙòè½R «=F¯
ÊÉ¥®½7z{`¾¤~-«,B-¸¦É®¹¼#°¤eUBjd«³½¡
¸¦É¥°ª°¤®½w»YV¸¾¤LöõæÐÒïéòÝîÕÐ×½6+íåÙòèÌ>É®¹¾$
¸¦É¥³®¸¤6+íåÙòèÌ_h¼>ɴü¤~p5ÌU ±ÉMV«h¼d§Ç Ê·§Éó%÷ô¥~-Ì[ª°´NT[,(Òïïäîè)Ì]¯²¤¢t½:¼~½p5Ì É¥®½p5¼U[X̨ɹ¤p5°·§´÷-«Ê·4|°¤6+íåÙòè«>ÇÊ É¥NT[,Ì]¯²·>ÇÊÉ~p5¾¤LæÐÒïéòÝî½8RÌ=F°·©È¤®
½¡R«6+íåÙòè=F¼¹»É¥³°·¤¨ÉU[X¼ÄWE«@¸¦É¥wU
¸¾6+íåÙòè«=F¯Êű§«¤áÛâÎòÅ(Ì͵[X¸¾=F_«C»É¥Á´¤í åÙòè=F_¾~-½o¼Ä.°¤*o½~YvÅjm\½£§ ~¸¾
m~«¨¡a-j¤«©j5\?LX¨
«ªN[Wj5=ªL[2]a-j|d¦ $Q
Ot[WªOtL[3,4]PEG b $gir+{Q $ 1©
XªBL[5]kirQj| A ¥ªBL[6]ª
ÉÌa-jJL
a-jJL".#½´Æ¿6:ª;LPSLªPSL¡KJÉ]e
X9KPSJ_l½´Æ¿mª;Lª[7]PS_lª}PS
n-jKJY-jgÉ$j½´Æ¿6:«ªÇÊAÈa-jJLG
qc 2ira-j6:K(¾¹Áï®Ã)sMQª 7+{
JRPµ¶»Å°§©@PSªPSL¡a-jJLI£0 T
ªPS½´Æ¿_lªw`*hJ]%ª¥Â½´Æ¿yUr) ª
&Dª¤PSKJYZª-jX9«¢9 -jg
(^É$j½´Æ¿6:«ª[8]
irÉ$j j¡¬Ë¸ºÀÆ·Ã`3 8fFvª¥ {±Å·Á²·!
>«ªu/ Cozp'¡p'ªEUr ,<V x±Å·Á²·!
A
B
Ê Ì ÇAÈ P S L H 4
ÇBÈPS :¼Ä³
²
K¥¼m7¹´A9]iº½¼,®5He±j¯¼ÇÛÑÙc¿¥¼®
m(¥¼¡±m7¿PQÆÛÎ×Éΰ(K£¨±m7»m7±(N
¿sk¯PQÆÛÎ×Éΰ(K£¨±A9]¼"à°6+ØÓËÜÕ±m7¹´A 9]¿o£¨m7²fd±yß-zQÆÛÎ×Éή¯»A9]²z
s®¯ª¬¼¡®¼µ¨y_D±{ÑÚÜп\£z¿º¦¼{1·
ÆÛÎ×Éο?¼¡®S¼OY®£¬i¢½¼
"àã6+ØÓËÜÕ±A1
* & ) ' % #
ØÁÙÌÂÕ1±b±³®«²A±ØÓËÜÕ¿L¼¡®¼"á°A3 ÄÖÏרܰ¹¼ØÓËÜÕ± <0¿o£¨ <$¿@£¬z±(>:¿^/¥¼¡®
z±=DeX¶º½¼[9]µ¨I£¨ØÓËÜÕ¿«Àlk±&G°À©»ØÓËÜÕ°
`c¿! ¨»t±L·x¼¡±¹¯ÔÂÅÚL¿|&²ÉÍÜȱrÉÒ Üɱ*s%±A¼µ¨A°#/£¨ÄÖÏרܲ0±J°8
°ME»J±4¯g'µ¨²J0¥¼¡®B~¼
"áã6+ØÓËÜÕ±ÔÂÅÚL
ÝÞ0}v±V;"ÝÞA3Ã
×ÉÄÖÏרܰ¹¼ØÓËÜÕ±
<ÄÖÏרܱn
µz <¢½¬¼
+ ' $
+ & ( ' ! "
uwz²)g'¸dF±(°C¤¬U¯>d¿»¼¡±¹¯*U¯zT ¿6 +ØÓËÜÕ1¥¼S¼"â²Z$°¹¼ØÓËÜÕ±>F(ÑÚÊɱ ¼
yß-z²z±D¿R£¬¼¨¶z¿£¨c±a:°¹»Z$h¤¼¡±
Z$7¿[¥¼¨¶ØÓËÜÕ²W¿£½£¬Wmq¿(¢¦¼Wmq(¥
¼¡®§½°2C¥¼./>Fp»(¾»ØÓËÜÕ*U¯>F¿p¥¼
%öøT&·ÀÃëâÖñåBH,àîÕÔ¸·8ª²# 8h
% ! # "
mqt·¹ÔßÈïÐsò·"ÇÓì)ÆL±ó´ÏíÔÙîñì£.¦¼ÄÃäÍîÜæÉï OsêßÛ£1'«Ã´p ÁIJÃò%÷óäÍîÜæÉï¹5×ïÞÍjÆKd·;
'©¬ÃGÆL±¨´¢ÁÓÎÝì¿:q¶µ¸*´ª²Qr«ÃäÍîÜæÉï¸s
0¹ÇÓì)¸G£J Áįg?^H·Â $¹[g?¶St³Ã¨¸täÍîÜæ ÉïÆ</ëâÖñå³OIª²z7«Ã¨´£³¤Ã%÷¹"s´"s´ÏíÔÙî ñì¸õI¢ÁIÃ</ëâÖñå¸vE³ÃäÍîÜæÉï´StĮķ;'«Ãô i¸vulÆV«Ã¨´³ëâÖñåw³¸ôRtOÆyª²Ã¶¡e=ðE
>Wj¸°§³¹t¸ÜæÉïOÆz7«Ã¨´¹N¶¼¯¨¸ôRtÜ æÉïO¹õRtB^´6·ËØà쪲¡ÂÜæÉï¸ÊïÜÑÉÛñÓÔ_£</ëâÖñå
·²z7©Ä²Ãò%÷ó[10]
%÷ømqtäÍîÜæÉïO¸PA%òó</ëâÖñå³_ª¯äÍîÜæÉïO¸íñÒñ
\ZEnu(£äÍîÜæÉïu(£St·8F«ÃÜæÉïÊïÜÑÉÛ ñÓÔ¸PA%
% ! $ "
a!¹]¸SÆ¥M4]¿]`dT·8«Ã+c´ª²stÆBIª²Ã
¨¸À¶çÚì3´ª²</ëâÖñå»a]¿2FÆ9«ÃãÉÍîËàÕì3
£}½ÁIJà º o|k´ ÏñܸàêÔäܸVYUÆb²ëâÖ ñåÆ X³xCõ÷@ÉïÌèáñÓéï·ÀÂ</ëâÖñ峸×ïÞÍIFàîÕÔ
£z7©Ä²Ã[11]¼¯ëâÖñå·9©Ä¯F]£-YU¸{l¢Á©Äè
´¾f~©Ä²¡Â</ëâÖñå£-]¢Á¸DQO´ª²M³Ã¨´£Å¢Ã
[1] Luisi, P.L., Walde, P. Giant Vesicles; John Wiley & Sons Ltd: Chichester (2000).
[2] Angelova, M.I., Soléau, S., Méléard, Ph., Faucon, J.F., Bothorel, P. Progr. Colloid Polym. Sci., 89, 127-131 (1992).
[3] Magome, N., Takemura, T., Yoshikawa, K. Chem. Lett., 26, 205-206 (1997).
[4] Yamada, N.L., Hishida, M., Seto, H., Tsumoto, K., Yoshimura T. Europhys. Lett., 80, 48002 (2007).
[5] Yamashita, Y., Oka, M., Tanaka, T., Yamazaki, M. Biochim. Biophys. Acta, 1561, 129-134 (2002).
[6] Akashi, K., Miyata, H., Itoh, H., Kinoshita, K.Jr. Biophys. J., 74, 2973-2982 (1998).
[7] Yamada, A., Yamanaka, T., Hamada, T., Hase, M., Yoshikawa, K., Baigl, D. Langmuir, 22, 9824-9828 (2006).
[8] Pautot, S., Frisken, B.J., Weitz, D.A. Proc. Natl. Acad. Sci. U.S.A., 100, 10718-10721 (2003).
[9] Evans, E., Rawicz, W. Phys. Rev. Lett., 64, 2094-2097 (1990).
[10] Hamada, T., Miura, Y., Ishii, K., Araki, S., Yoshikawa, K., Vestergaard, M., Takagi, M. J. Phys. Chem. B, 111, 10853-10857 (2007).
[11] Nomura, S.M., Tsumoto, K., Hamada, T., Akiyoshi, K., Nakatani, Y., Yoshikawa, K. ChemBioChem, 4, 1172-1175 (2003).
R;V0303g"f;3nqpg"E+6J
|
oÂe'¢R;V0303g"f;3nqpg"E+6JÁ7k}fKIÁnq4»¢c nq$ϱº©Ëų¢|¼i±Å³£2006?3Q¿R;V0303g"f;3nqpgb ðùâá6JÁ#KIÁǼ»3ÏB±¢!?4QÉËÑóöØ &ØöïÖ÷ëÑ:ÝúêÒ ÕÜÁáÚöðánqGÁProf. Jeffery W. Kelly nq4¿ý?-nq$¼±ºj3±º¦Å±·£
¯Á·Ä¢j3Á)uÁZϦ·¸¬Å±·Á»¢ÝúêÒÕÜÈáÚöðánqG¢Kelly nq 4¾½Áx ϱ·¦¼D¦Å³£
ÝúêÒÕÜÂùÝúã÷áÁw 200Ùù¢ÑóöØPs¿¥Ì¢v»t 7¢ØöïÖ÷ëÑ:
»ÂÝúïõúßáÛÏH¦ºt 2 Á Y»¥Ì<»³£1>^]9¢?ϱº°±
ȳ¦\»O³Çµ´5³Çµ´¢=.¾ÊÀ=N¼¦¹·F»³£M¢Â8È
«¥¹ºÂ«¹ºáÙü«W±ÆÅ³±¢m`È~(Ç¥¹º. 40¡A¼¦¹·¾,GÇ
¥Ëų£=¿{a«ª»X¤¾øàôü«W±Æ¢S¨·0<»Ç¥Ì·Æ¢America's Finest
City ¼§·Îͺ¦Å³£
ǼǼÝúêÒÕÜ¢*(Á¼±ºS¨º¬·Á»³«¢?»Â¢íÓéÚhV<¢nq3
<¼¦¹·«@®¾¹º¬º¦Å³£ØöïÖ÷ëÑ03ÝúêÒÕÜT(UCSD)Ïu¿¢ÝúêÒÕ Ü:r03(SDSU)¢äüÚnqG¢¶±ºáÚöðánqG¼¦¹·KzûnqZ«C¼¾Ë¢E+
VÈ¢îÓ×¢¢lZ%ÁV¾½«y±2ƺ¦Å³£g"3»¨Ã¢ïÐ ÓÞü¢ó÷Ú¢ìî÷éÒá¾½Á0VϲƢL/®ÁñúçôüV«áÚöðánqG¿
Źº¦Å³£
ÝúêÒÕÜ_¼ÝúêÒÕÜÁæÔúåÔú áÚöðánqGñèÚòúU[d áÚöðánqGñèÚòúU
įĩőŃᡦjĐîĭŕķġĤĬď*ďŐņŎċñò¼ĎðĚîĠŌőħ}Bď¢§¡¦ ÞďćĊî 300 Ïñu5ċî800 ĒČďňįĹĩċ100 ¤YďEî1500 ď³5ĊgýĜĉñēĀï}ÏĊ Đî2001WĎĮōŖŃœįurî2002WĎŁŏŖĸőĵŀuröĽŖńŒ)EÉĞ/Éþî)Eď¡¦Ďô ñĉ}Ė]è'öðě¡¦jċñĝĜĉñēĀï
ë ď@ďBEė9@ď¡¦ ÞöČòčďõĐĘø#õĚēĂğöî¢ö{~ďBEċĐÕòċfÿ ĄB÷čĐjďňįĹĩď&1öçUĎAñüċċî2¡¦öçUĎAñċñòüċöoûęĜ ěõċbñēĀïēāćĎÞþĉĐjďh'öňįĹĩĊðěċñòüċĖðĚjĎôú ěňįĹĩď°ĈúöþĆõĚþĉôĚî롦ď=öwýĜĉñě.ÆĞ/úēþĄïóđî ňįĹĩďĄĕĎĭŖĩŒėĿŖĶġŖîP³ÃėĨōőĠĠĵŃďĄĕďP³ĎÞĀěıŊĺŖî¥Ú ėãčČďĎÞĀěıŊĺŖčČöðĚēþĄïüĜę롦ĞÑþĉîňįĹĩ2>ďćčöĚĖ[
øčĚîăďôâõČòõĐ#õĚēĂğöîŌŖőŕĪőįĸ(ML)ĖçUĎğĊþĄïrėıŊĺŖîº čČďÑ ĞĀě¶d<ď ML ďĒõîËėKčČď04Ğ ?ÇĀě MLî 6ėÁ¸ď ÈþĚėHéďėĚzčČвúě¡¦ĎÞĀě ML čČöðĚîÓÝŌŖŐŖď/¨ĞtĆĉôø ċŌŖŒöîċēĚ׿$ĜčøčěĒČĊþĄïēĄî¡¦IďqáîĬŊpĉîZ!î ýęĎi¯ĚēĊĖî³5ĎĂěüċöĊ÷îEėňįĹĩĐ¡¦ĎMaĊ÷ěüċĖê÷ĊþĄïüďĘ òĎîňįĹĩėEöė¡¦Ğ ĎºóěĘò¡¦jĊĚûĉñě.ÆĞ/úēþĄï ë ¬ñĉ2¡¦ďAýĎćñĉĊĀöĎÞĀěMLĎÆ^ýĜěĘòĎçUĎ¡¦IÝď;ö ñüċöîăďċþĉoûęĜěõċbñēĀïňįĹĩąúĊčøEĊĖԺ`¾č Å ėl»ĞĖćď¡¦±ċÂþ1ĆĄĚîñď¡¦IďıŊĺŖĊ½þðĆĄĚþēĀïăþĉîñ ď¡¦Iк÷þĉHéĀěĘòĎčĚîýęĎ2¡¦ď×QĎĖńŕĴėĞĖęòĘòĎčĚî}
ªĎĐÄxčČĎ·Ċ½ĀěċñòüċĎčĚēĀïüďĜĐ¡¦jąúĊĐčøî¡¦E»Ø Tď:ď%ĞõþîñĉĀùºúěIJŖĩ¡¦jėËĊ10#ďUCSDîčČċď2¡¦Ėğ ĎºĝĜĉñēĀïHäµ#ösĝĆĄ 3 ćďĶŖʼnĊĖî1ćĐ¡¦jĊď2¡¦îĖò 1 ćĐIJ Ŗĩ¡¦jċ2¡¦ĎčĆĉñēþĄï
ë ďĘòĎî}ÏďįĩőŃᡦjďRċg(Đî,ĎŁĵĪļŖŋďuràďLċñòąúĊ ĐčøîňįĹĩĞòēøñIÝď;ĞøĀěüċĊîyþñĶŖʼnėeö͵čæ8
ĊĔ"ýĜěüċ롦IĊĐÔº7å衦Ğ2ĊÌĎºóěċñòüċĖĊĐčñõ ċbñēĀï
Prof. Jeffery W. Kelly
Kelly¡¦IĊĐîijŕĿĩÊďłĥŖŒķġŕĪėŊįłĥŖŒķġŕĪĎÞĀě¡¦1)кĆĉñēĀï
ĠŕĴĿŐœŒíĮŖĸÒĞFGĎċěŅŃĴĹďÜĎCēĚîĦœłġŕîĤįĶŒ«1ĞÛĎN þĄíĮŖĸŅŃĴĹďłĥŖŒķġŕĪĞÀĀě¡¦îÎÐijŕĿĩÊTransthyretinďĠŊŔĢĹ\g ďŌħĻİŋÀ|ċăďĠŊŔĢĹ\gĞßJĀěO#DĊðěīŊħŒĮōŅŔŕďÜĎÞĀě¡¦î
Gaucher čČĎôúěīŊħŒĮōŅŔŕď¡¦čČöoûęĜēĀïÏWĊĐîAlzheimer amyloid
-peptideŗAŘďĠŊŔĢĹ®)ĎÞĀě¡¦ėîì-synucleinĞ_ċþĄParkinsonĎÞĀě¡¦Ė
ºñî)E#Ùõę©´ėʼnģįĞĆĄ#ÙēĊVXñkĞñĉcė®)ŌħĻ İŋďÀ|čČĞnþĉñēĀïĎî}ÏĐ#ÙĎ'ĞñĜĉñěĂñõîEĞ3ĕŐŇďŌ ŕľŖď+vĐî)E£ĊðĚčöę©´EėÖDSEčČĞľĵĩĪŐģŕĹĎmć Ċ-
íñôßÈêÕÅfòç_e%;àÄïėĕċĐãâævÂ:öPÜßÈÙĝģēĦç ö,íß TòÔÌÈãÈtjàÔÙÅĞĘædNç#U ĩÄęĈĐāĮÄ;vĭÄQ.ĪÄ\ĩ àÄøĝğÿ7æ72Í8ÈĈāğĕĈàçíÖñÔÐÄøĝğÿÍĮáµ'Wö(íÄ2ĬÄ úģĐÄĆģĀęĦĠÄĈûüĦďģľ2ÄZaħ ĨÍ*ĩàÔÙÅ
à ÍSEÔÙĎĦĚçīÝÇòêÕÍÄâôîAä»ÕóàÔÙÅ 0çÄØæÉÛæĝúģà´Ô ßÈÙĎĦĚä»ÔßÈÙÔêÕÅøĠčĒúĚĦ|æ)1r«áÊñôßÈó AæøěĢúĐ
%äËÈß AævpDç nMġĖĠá õôßÈêÕÅYÄAæ½ÔÉó]pDħ¼xp DĨçWμM !Gá õôßËòÄvæðÉãg®~pDäËÑó Aæ½FNĝÿđĉĜç`Ú
[ÓôßËòê×÷ÅKelly>àç!ðòÄv{B¨¹%r«ÍAæ½ö³Ó×óá ÈÉöÔßÎêÔÙ 2)ÅØÒàaàçÄøĠčĒúĚĦ|ä»±ÔÄv{B¨ràÇó áÊñôßÈóăġĈĎĢĦĠ¹%rö¸s{~äÀÔÙAö¢¡ĥ+NÔÄvæðÉãA pDu5àæ½FNäÝÈßðò¤ãbö£ëêÔÙÅVäðó½FNæ°Dm<ïÄ
½FNæ¼xpDæö£ëÙcÄÀAàçWnMįW& nM ġĖĠàæ½FNÍñôÄ
¼xpDÍWμM!GàÇÜÙ`ÀæAðòîÄÌãòÈpDà½ÕóÒáÍÌòêÔÙÅÓñäÄ ăġĈĎĢĦĠ{B¹%ræÀæ·ÈäðÜ߼FN°Dï½FN¼xpDä6%Íñ ôêÔÙÅaàHñôÙçväËÑó Aæ nM ġĖĠàæøěĢúĐFNĝÿđĉĜæ[
äÝãÍóáÊñôêÕÅ
à ĎĦĚçĘĈá¦ÔßiêòêÕÍijíYãâçäÓôßÈêÕÅe/æÈYï=Á æOkãâçĞĘæĝģēĦÄsä;vÍÔÜÌòÔßÈßðÐUÊßîñÈêÔÙÅĞĘæěĦĎùģĂͲ ä 1 0Ä3 Ĥ^ä0éâæ"+àæ}ÍêõÜßÎßNcö4-ÕóéÌÄ äĘĈï#Uá
³tjï=Áæ¤äÝÈß©§ÕóeîÇòêÕÅEçÄÙðÉãĎĦĚöÉĝģēĦÍĞĘ äçfÜßËñÖÄ=Áö¶ä×óæäîÄ¥àÆá@åUõóæäî$ÔêÔÙÅáÌ=Á ö¶ä×Ä¥àæ=Áæ©§îðÉïÐLô9íÙ¿äçÄ2 Cºn3æõòä¯ÞÈßÔêÈ êÔÙÅA2êàä§X}çºä+Èê×÷àÔÙÍÄRêàçoÏÑêÔÙæàįÈÉÛä}
ÓôôèáJÜßËòêÕÅ
ąģďùýĄàævläËÈßzyKÔßËÌãÑôèãñãÈÒáçÄ2 qÇóÌáJÈêÕÅÝ
çÄ?ªÍÂÈÒáàÕÅAmerica's Finest CityáÈÉÒáàÄìÒáäMôöîÝøĝğÿÍ8Ðh ÍÂÈÒáÍ1àÕÅ1 ĖČĐĠĦĜïĈĊćþàî^$1000 ÕóæàÄOöÕóá^æ' Í?ªáãóîÈêÕÅêÙÄĠĦĜĆüøî÷äõôßÈêÕÅÝçÄ?w¬ÍIáÈ
Prof. Jeffery W. Kelly Kelly>æĝģēĦ āğĈĚĈĔĦĎùĦàZaæYÆá
¥¤Finest City¥f¶µ£´¨¯¶²qÑþ§¦©uCªn-¤q´©¥
§©¥¤ªKH¯§³x¡¯©¨§³·»Î¹µ«KHª+¨°b¤
DrPG(_¯²¤>Y©¾ÒÄÒO¼ÌÀÆÓ$1.5Ô§¦¯³>B;
J>B©o¯¬¥¸¦5¨³t,{a°NE TÑh T§¦¤¯>Bi
u´C #§³ÂÍÅÏ¡£¯£ª)?¨eF¤´±¨§¡£Ó
`iª¡w§§³Ô
²¨I¨'U¨£ª>BRV]¥©¢§³¯.zªx¡£¯RVÑKH§¦©
¤¡£´¬ÄÒÁºÒ°=a§¦¨¯aC ³M'/²¾ÊÒ¿¨KH
RV·%®´¥¤©¯©¾»Îƾ>BRV]©ks<©¤§>B¨*
0¯¢§³³>B¾»Îƾ ·u£1,¨1ªW ÑRV }µ£³È ÒÊÇÒ½ 3)¯³ ²©M'3 °M'gªM'©^¨¥¡£¯$"\¨§³
©!·³£>B¾»Îƾ ©kK<¨S·L
2 ,~©M'ª|±¨2¡¥~¨v£¡m¤©Q±¨
4´A~¨1²µZª+¨py§¯©¤0©RVKH¨K£µ«¥2
@0¨§³6`i¤¯d¨8£¡Kelly97¥ÍÉ©ËÐÃÒ¨4l
M'g©X©C ·£[&©K<¨SL
1)@t©cP§j:¥£Johnson, S.M., et al., J. Med. Chem., 48, 1576-1587 (2005); Fu, Y., et al., J.
Am. Chem. Soc., 128, 15948-15949 (2006); Cohen, E., et al., Science, 313, 1604-1610 (2006); Bosco, D.A., et al., Nat. Chem. Biol., 2, 249-253 (2006); Fowler, D.M., et al., PLoS Biol., 4, e6, (2006)§¦
2) Zhang, Q. et al., Proc. Natl. Acad. Sci. U.S.A., 101, 4752-4757 (2004); Bieschke, J., et al., Acc. Chem.
Res., 39, 611-619 (2006) §¦
3) http://www.geocities.jp/japan_scripps/
¸ [email protected]