ABC
!"
#$ %&' ()*+,-./0$
12 ABC (AATP-bbinding ccassette)3' ABC456 7 - %&' ()*#891:%- ;#<=>0?@2 ABC3'ABC./@D EFGHIJ(NBF)K1+ LM@N!OPO"
3'63QRSTMN U4#A48V@A49 ABC3'-W91 #12
$%=X Y6 &AZ'(#[)\*]K^@
_ V@ &' +`A&'Eab '(#,-TM 12 .TA%&' ()*+,K LEabT/c 91@d# Y6 &%&' +` 0e#==<
1ABC3' f1Kg>@2
Vhi2# Y6 ⋔bjkb3456
(SUR)%DEFG 7lmKf1#c8_D
EFG#B1SURKn_@ATPo5pqGrsb KATPGrsb 0e Lt9K2d0:X=#_@2 .X
# ABCG3'#B1u;"&' <=%ABCG 3' u;vWKc8_ &'>?+,%vW'(+
,K:X=#_@2 .#B>0@X/@ABC3'
#B1%&' ()* L+,#891A)\BwK Cn912
1. ABC
KATPGrsbA ABC3'#D91SUR%Grs b7xyz{k4Kir6.2=X,E./ u;F|GHK oB_0I}f1J~#K912 SUR#AyzY- W_SUR1/Kir6.2KATPGrsbA$bu;TY6 &'(# SUR2A/Kir6.2, SUR2B/Kir6.2KATPGr sbA//L%M TZ u;#NC2 $b
u; KATPGrsbAOGHTA_0"IK)*_
0N Z-PQ91% ZRb6-u;#N
V/F|./0ATPST PQADPST UKP@X 9 #22$bu; KATPGrsbADEFGST K fKoB_0V_ "-W _ /-iX1#Y6 &K?:92 SUR1 YL-ZUZ[K P@X9:% iPC$X/13\]TM16bj kb34 ^1 L-SUR1TM1:%=X SUR c8 A8L-P@/0$12 _=_ I}/1c8A./0$
@-f1c8A_TXhKATPGrsb DEF G#B10e L+,A`:TM>@2 DEFG#B 1Grsb 0e+,K:X=#91@d SUR !O NBF (NBF1, NBF2) DEFGHIaKb_@2 ATPcTM18-azido-ATPK$@de^ ¡¢
=XSUR NBF1-£deATPHIfNBF2-Ud eDEFGHIfTMN NBF2 ¤#ATPgc -M1:%!O NBF¥#¦'-M1:%-<=>@2 .X# NBF 1 DEFG#h91de-SUR 2 A, SUR2BBNSUR1T£$:% NBF2 de-SUR2AB NSUR2BT£$:%K:X=#_@2 :/X H^=X /1\u;ATP, ADPSTTA SUR NBF 1#ATP, NBF2#ADP-HI_@§TGrsbKf91¨©bK ª_ SURyzY¥ DEFGHI «$#B>
0KATPGrsbyzY¥ a «$-P@X./1¬
Kª_@2 _@->0 SUR-u;ADPST KfK oB91y L%_0+_ GrsbVK0e91 :%-/1#A)TM1:%Ki®T2d0:X=#_@
#32 V@ SUR1 KAZUZ[KP@X9-
K ¯O(R1420C)TA NBF¥ ¦'-°</
1:%K:X=#_@2
1 ABC3' !±,j%KATPGrsb ,j ABCA1K²³kC ABC3'A12´"µl J%!O NBFKPO2 SURA17´"µlJ%!O NBFKPO2 ABCG 1, ABCG 5, ABCG 8ANmn#
¯O NBF%Cmn#6´"µlJKP¶!oT +912 KATPGrsbASURyz{k4%Kiry z{k4=X,E./ ·¸poK§E_0+
912
2 $bu; Y6 &+,
UZ#Au; ATP/ADPq-UC KATPGr sbA_0"IK)*_0$12 £Z#A -NV/F|./0 u; ATP/ADPq-£C
\N KATPGrsbAV912 H^ u;"-W _I¹pbqGrsb(VDCC)-
_ pbq rs% Y6 &-:12
5t"º»)¼ ½fuvt 33
2. ABC
ABCG ABC
!"#$ %&'4()*+ ,-./0
ABCG1 ABCA112345
(HDL)167 !8#9) 3:
;ABCG1<=>?@*? 6A*
+ ,# !#%&B1CD ABCG1:#EF&G DCH&) ABCG51ABCG8I! !JK"##L 6 MDR3 (ABCB4)ABSEP (ABCB11)12$MNO!
#9) ABCG5ABCG8 P%&Q%R&
S#TU '( !%&)*+,-Q%
.V@ !W/XYLZB[\&B1X0D\]&) ABCGX:^)_`#G1ab%
B1X23[\XABCG:cd1#e cd4 HUfABCGg10 hij)
2.1 ABCG
ABCG1k56l7(890m: ABCA1k 56l01;nXD 8<=#>?[\&:>o
@) ABCA1X !1 +p,!4
>545A-I#"%&#AABCG1ATP qB>orC# !1 stNu4 HDL#"%&B1 DC# '5() ! 1 stNu40Dv@1wx\&NPy
%&) ABCA11ABCG1Xz\{\<v@
v@#hi%&B1 ABCA11ABCG1:"|
0 stNu41z\{\8E$ E$%&B1 } ABCG1:"cdXABCA11S&B1
DC#)ABCG16l#TU0D
!X~F[\&B1}) B\DbCD
ABCG1X0Dv@:%&B1])
2.2 ABCG
ABCG1, ABCG2, ABCG40D#hi%&
#A ABCG5ABCG8I#h
i #Uf0D#%&B1 DC#) I! !0 ABCG51ABCG8
XGHDI#6l $MNO!7
!1'( !"#9B1}) [D# ABCG 1, ABCG21ABCG5, ABCG8yvJ0
hij ABCG5, ABCG80KX
IL#$ zK#MERL8V
!NOXCi%&P} '5()
Q R^)_`#$ %&SURpP
S DC# SUR#T&KATPp!|cd1z
\{\SUR#e !T") [D#
:^)_`#$ %&ABCG#T&g U5 :cd1hi#ecd}) VWL XY1U]&y4=VP #A%&Z[
6A.\2]%&f^6# _b
¡¢£]L]) cP4 ABCX`9 Ci%&B1CD z\DcPo@Xafx R1 3 SUR#T&KATPp!#e !
SURNBF 1#ATPX NBF 2#ADPX1 Lp!X|[\&) 0ATP, ADPbXz
\ { \cq ¤ ¥ % & 1ADPXNBF 2C D od ATPX p!4|[\&) ATPXqB
>o[\&C odADPXNBF2# ~¦
p!X|[\&) SUR|§14|§e
¨$©#Hª SUR0ADPbO 1 9)
4 :%&ABC
(= !1$MI!CDJK[\«
#¬N67x\&) 6CD/
07LDL1 !x\ /0
!HDL1678[\
&) 6CD !H&]$M#&®[\
¡ $¯7"[\&) fg::°±
XD\&) `9ABCX:
#$ ]&)
5 :^)_`#9ABCGcP1hi
#e
I!16ABCG5/ABCG8X²7 !
"#9) ABCG 51ABCG 8I (ER)#L ³X0D#
!"%&) ABCG5, ABCG80K#M
ERL8V!XCi%&PXH&)
/0 ABCG1X0D#
hi !1 stNu4"%
&)
´ hµ¶·ij ¸ ¹jº»¼½
34
!"#$% &'()()*+)"#,-.,)/012 .3)"#4567895 !"#:6;:<=
>?@% ABCDE=8?8&'()Fῌ12GHI JKLMNOPQ()*+)"#,RS TUVW.X 8E 8% ).YZ[\CDR]5^@_CD8
?8&'()RS `abcW.d[\eX8E &'()()*+)"#,fRS ghiW.$j>
klmno:p8:eX8E \% qrs Jtuvw()RSFrances M. AshcroftW.%xy()()
*z){"#,RS | }W.% &'()()*z)"#
,RS ~W.% &()()*){"#,RS
W.% &()()*+).,)"#,RS
W.% e"#123) UW.%
()()*z)"#,RS W.:$
EE8j>"#>eX8E !
"#$12.3)"#4.% ¡.¢£^=¤\
8¥¦5^@% "#4§¨>eX8E © % !ª«_¬>?E8®!+¯3);§°¢
!±²W.% m\Q_¢£p8³W.>´µ E¶·