61
Newsletter- 生体機能関連化学部会- Vol.34, No.2 (2019. 12) 1 Newsletter 巻 頭 言 生体機能関連化学部会と私 二木 史朗 2 Award Account 部会講演賞 植物ホルモン共受容体サブタイプ選択的アゴニストの開発と植物免疫制御 高岡 洋輔 4 核酸の代謝的ラベル化と近接効果を利用した高速クリック試薬の開発 寺 正行 9 非環状型人工核酸 aTNA の高速かつ高効率な鋳型特異的ケミカルライゲーション法の開発 村山 恵司 17 主鎖アラニン型ペプトイドの配座安定性評価と生体分子認識への応用 森本 淳平 23 Award Account ポスター賞 小分子リガンドによる細胞接着蛋白質 P-カドヘリンの分子間相互作用制御と構造情報に基づくリガンド 設計 妹尾 暁暢 28 線維芽細胞増殖因子受容体の活性化を制御する機能性核酸の開発 江口 晃弘 30 photoSLIPT による細胞内分子の光操作と多色イメージング 沖 超二 32 RNA 高次構造形成に基づく新規遺伝子発現制御技術の開発 嘉村 匠人 34 1 分子酵素活性プロファイリングによる疾患関連酵素の超高感度検出 坂本 眞伍 36 リガンド指向性化学による NMDA 型グルタミン酸受容体の選択的なラベリング 白岩 和樹 38 Ru 光触媒担持アフィニティービーズを駆使した抗体の Fc 領域選択的化学修飾の開発 中根 啓太 40 糖分解酵素活性検出蛍光プローブ群の開発と悪性及び良性腫瘍特異的蛍光イメージングへの応用 藤田 恭平 42 生体分子の網羅的イメージングを可能とする蛍光バーコードの開発 牧野 航海 44 ぶらり研究室の旅 萩原 伸也 46 部 会 行 事 第 13 回バイオ関連化学シンポジウム 開催報告 和田 健彦・珠玖 仁 48 市民公開講座「生活そして人生を豊かにし、社会に貢献するバイオ関連化学最前線」開催報告 和田 健彦 52 第 13 回バイオ関連化学シンポジウム講演賞 講評 上野 隆史 56 お知らせ 第 13 回バイオ関連化学シンポジウム講演賞・ポスター賞 58 生体機能関連化学部会ロゴ決定 59 第 14 回バイオ関連化学シンポジウム会告 60

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201912v51
Newsletter
NMDA 38
Ru Fc 40



59
2



1970 80

3


4







2014 72016 10 JST



2 PPI
PPI Fig. 1a 1[5-8]

Newsletter-- Vol.34, No.2 (2019. 12)
5




[9] 2. COI1-JAZ in vitro in silico JA-Ile COI1-JAZ
COR, 3
COR JAZ
[10,11]COR
CFA, 4
CMA, 5
4 3, ent3, 6, ent6, Fig. 2 COI1-JAZ9
Y2H4

[11] ent6 Y2H COI1-JAZ9
JAZ COI1-JAZ
Y2H Y2H
COI1-JAZ

JAZ
JAZ

Figure 1. (a-c) a: [2]b:
[3]c: [5]. (d) 1 JA-Ile2
COI1-JAZ .
6
COI1-COR- JAZ1 X [5]COI1
JAZ1 COI1-COR Jas motif

JAZ Jas motif
anti-Fluorescein JAZ
JAZ1 GST COI1 COR3 COR
ent3anti-Fluorescein anti-GST
Fig. 2aCOI1-JAZ1 COR JA-Ile PPI ent3 JA
COI1-JAZ PPI Fig. 2b 4 COR Jas motif
JAZ COI1 PPI COR COI1-JAZ
ent6 COI1-JAZ3, 9-12 5 PPI ent6 in vitro
JAZ
COR-JAZ1 JAZ in silico docking study
COR
ent6 COI1-JAZ3, 9-12 COR
Figure 2. (a) OG JAZ pull-down . (b)
. (c) COR . (d) COR COI1-JAZs
(I.S. = ).
7

NOMeNOPh NOBn
JAZ
NOPh8 JAZ9 10
13 JAZ 2
Fig. 3b 3. COI1-JAZ in vivo 8
1 COR
ent6 8

8
PDF1.2 COR 5
ORA59
50 µM 5 A. brassicola COR


Fig. 4[9] in vitro JAZ9/10
in vivo
JAZ
ORA59 jaz10-1 mutant
jaz9-1 mutant

Figure 3. (a) ent6. (b) ent6, 79 COI1/JAZ .
Figure 4. COR (3) NOPh (8)
(a) (b).
8
[13] 8 COI1/JAZ9
ERF1-EIN3/EIL1-ORA59 MYC
COR JA-Ile
in vitro JAZ

JAZ 4.
2016 Greg Howe 13 JAZ 5 5
6
[14] 10 11 JAZ jazD, jazU[15] JAZ


[17] ITbM
Bump-and-hole [18]


2018 in silico
Roberto Solano Andrea Chini
JST JSPS
[1] Jiang, K.; Asami, T. Biosci. Biotechnol. Biochem., 2018, 82, 1265. [2] Murase, K.; Hirano, Y.; Sun, T.-P.; Hakoshima,
T., Nature 2018, 456, 459 (PDB ID: 2ZSH). [3] Tan, X. et al. Nature 2007, 446, 640 (PDB ID: 2PIQ). [4] Santiago, J. et
al. Nature 2009, 462, 665. [5] Sheard, L. B. et al. Nature 2010, 468, 400 (PDB ID: 3OGM). [6] Thins, B. et al. Nature 2007,
448, 661. [7] Chini, A. et al. Nature 2007, 448, 666. [8] Fonseca, S. et al. Nat. Chem. Biol., 2009, 5, 344. [9] Takaoka, Y. et al.
Nat. Commun. 2018, 9, 3654. [10] Okada, M. et al. Org. Biomol. Chem. 2009, 7, 3065. [11] Ueda, M. et al. ACS Cent. Sci.
2017, 3, 462. [12] Song, S. et al. Plant Cell 2014, 26, 263. [13] Zhu, Z. et al. Proc. Natl. Acad. Sci. USA 2011, 108, 12539.
[14] Campos, M. L. et al. Nat. Commun. 2016, 7, 12570. [15] Guo, Q. et al. Proc. Natl. Acad. Sci. USA 2018, 115, E10768.
[16] Halder, V.; Russinova, E. Nat. Chem. Biol. 2019, 15, 1025. [17] Vaidya, A. S. et al. Science 2019, 366, 446. [18] Uchida,
N. et al. Nat. Chem. Biol. 2018, 14, 299.
Newsletter-- Vol.34, No.2 (2019. 12)
9

2011–2012
2012–2019
2016–2018 Nathan W. Luedtke
2019 7





BrdU DNA
Fig. 11BrdU 5


10
5-ethynyldeoxyuridineEdU
DNA 2EdU Huisgen Copper catalyzed Azide-Alkyne CycloadditionCuAACDNA
CuAAC
3 DNA
4CuAAC
DNA 5-azidomethyldeoxyuridineAmdU
dimorpholino- cycloocadiyneDiMOC DNA

2. POM-AmdUChemBioChem, 2018, 19, 1939. Luedtke 5
AmdU 5AmdU Strain-Promoted Azide-Alkyne CycloadditionSPAAC 6
AmdU
NH2 O
PO OPh
NH O
OAB I2, pyridine
OAB O
11
HINT-1 ProtideProt10
Scheme 1AmdU DNA
3
HeLa 24 DNA
CuAAC DNA Fig. 2
POM-AmdU AB-AmdU DNA AmdUProt- AmdU HeLa AmdU
HINT-1 AB-AmdU HeLa
U2OS 12
AB-AmdU POM-AmdU AB-AmdU 2
AB-AmdU
11POM-AmdU DNA
POM-AmdU U2OS AML
POM-AmdU

Fig. 2 AmdU POM-, AB-, Prot-AmdU 10 µM HeLa
24 . 2M HCl DNA AlexaFluoro-594-
Huisgen DNA . POM-AmdU
DAPI.
12

DNA

2 122010 CODY
SPAAC 13

Scheme 2 8
14 DiMOC
DiMOC X
CODY
DiMOC
> 10 mM DiMOC DNA DiMOC DNA
DNA DiMOC UV
DiMOC DNA 3 1
15 µM DiMOC AmdU
1.0 M-1•sec-1 DNA
DiMOC DNA

BCN-TAMRA 50 4%
AmdU BCN
Scheme 2. Dimorpholino cyclooctadiyne (DiMOC) . NBS = N-bromosuccinimide, AIBN = azobis(isobutyronitrile), DIBAL-H = diisobutylaluminium hydride, LHMDS = lithium bis(trimethylsilyl)amide, LDA = lithium diisopropylamide.
CO2H
Me
LHMDS, ClP(O)(OEt)2 -78ºC
ON NO
13
ODN-1 DiMOC N3- TAMRA ODN-1 5

DNA
DAPI DiMOC
AmdU


2'(R)-azidodeoxyadenosineDNA
Fig. 4 RNA 2'(R)-azidodeoxy adenosineDNA AzC
.
Fig. 3 a) DiMOC AmdU DNA SPAAC . b) BCN-TAMRA N3-TAMRA
. c) AmdU DNAODN-1 BCN-TAMRA DiMOC/N3-TAMRA
. ODN-1 T AmdU . d) POM- AmdU HeLa BCN-TAMRA DiMOC/N3- TAMRA DNA .
Newsletter-- Vol.34, No.2 (2019. 12)
14
DiMOC N3-TAMRA RNADNA
AzC DiMOC/N3-TAMRA DNA AzC
15

3-2. DiMOC DNA Angew. Chem. Int. Ed., 2018, 57, 15405. Cis-Pt DNA-DNA ICL

POM-AmdU DNA 2
DiMOC DNA-DNA
AmdU DiMOC ICL
Fig. 5 ODN-2 AmdU ODN-3
AmdU Fig. 5a
ODN DiMOC 2 ODN-2
Fig 5b, lane 2 MALDI-MS ICL Fig. 5c 2.1 x 105 M-1•sec-1
AmdU DiMOC 10 DiMOC
DNA HeLa POM-AmdU 72
2 PD time = 30 DiMOC
ICL
denaturing-renaturing ICL POM-AmdUDiMOC
Fig. 5 a) DiMOC AmdU DNA ICL . b) ODN-2ODN-3 DIMOC
. c) Lane 2 MALDI-MS .
Newsletter-- Vol.34, No.2 (2019. 12)
15
DNA 100-300 bp DNA

ICL
Fig. 6aICL
POM-AmdU DiMOC DNA S1
Fig. 6b, lane 8, 10, 12
UPLC-MS ICL
Fig. 6c, dAmdU-DiMOC ICL
DiMOC POM- AmdU DiMOC

DiMOC SPAAC
DiMOC

Fig. 6 a) DNA ICL denaturing-renaturing . b) DNA
denaturing-renaturing S1 . c) S1

UHPLC-MS m/z=513.20–513.21 SIM . d) ICL .
Newsletter-- Vol.34, No.2 (2019. 12)
16
POM-AmdU DiMOC DNA
POM-AmdU HeLa IC50 > 100 µMDiMOC DNA BrdU EdU
DiMOC
Department of Chemistry, University of Zurich Nathan W. Luedtke McGill UniversityLuedtke DiMOC X
Tony Linden University of ZurichUPLC-MS Jorn Piel
ETH Zurich
Dr. Helmut Legerlotz Foundation [1] R. C. Leif, J. H. Stein, R. M. Zucker, Cytometry 2004, 58A, 45–52. [2] A. Salic, T. J. Mitchison, Proc. Natl. Acad. Sci. 2008, 105, 2415–2420. [3] D. C. Kennedy, C. S. McKay, M. C. B. Legault, D. C. Danielson, J. A. Blake, A. F. Pegoraro, A. Stolow, Z.
Mester, J. P. Pezacki, J. Am. Chem. Soc. 2011, 133, 17993–18001. [4] S. H. Chiou, J. Biochem. 1983, 94, 1259–1267. [5] A. B. Neef, N. W. Luedtke, ChemBioChem 2014, 15, 789–793. [6] N. J. Agard, J. A. Prescher, C. R. Bertozzi, J. Am. Chem. Soc. 2004, 126, 15046–15047. [7] M. E. Black, L. A. Loeb, Biochemistry 1993, 32, 11618–11626. [8] D. Farquhar, D. N. Srivastva, N. J. Kuttesch, P. P. Saunders, J. Pharm. Sci. 1983, 72, 324–325. [9] W. Thomson, D. Nicholls, W. J. Irwin, J. S. Al-Mushadani, S. Freeman, A. Karpas, J. Petrik, N. Mahmood, A.
J. Hay, J. Chem. Soc. Perkin Trans. 1 1993, 1239–1245. [10] C. McGuigan, R. N. Pathirana, N. Mahmood, K. G. Devine, A. J. Hay, Antiviral Res. 1992, 17, 311–321. [11] J. L. Bolton, Curr. Org. Chem. 2014, 18, 61–69. [12] H. N. C. Wong, P. J. Garratt, F. Sondheimer, J. Am. Chem. Soc. 1974, 96, 5604–5605. [13] I. Kii, A. Shiraishi, T. Hiramatsu, T. Matsushita, H. Uekusa, S. Yoshida, M. Yamamoto, A. Kudo, M.
Hagiwara, T. Hosoya, Org. Biomol. Chem. 2010, 8, 4051. [14] F. Xu, L. Peng, K. Shinohara, T. Morita, S. Yoshida, T. Hosoya, A. Orita, J. Otera, J. Org. Chem. 2014, 79,
11592–11608. [15] T. Triemer, A. Messikommer, S. M. K. Glasauer, J. Alzeer, M. H. Paulisch, N. W. Luedtke, Proc. Natl. Acad.
Sci. 2018, 115, E1366–E1373.
Newsletter-- Vol.34, No.2 (2019. 12)
17



DNA RNA

GNA[4]
XNA
D-aTNA (acyclic D- Threoninol Nucleic Acid)[5], L-aTNA (acyclic L-
Figure 1.
18
Threoninol Nucleic Acid)[6], SNA (Serinol Nucleic Acid)[7] 3
(Fig. 1) D-aTNA DNA RNASNA
L-aTNA

[8]
XNA XNA

XNA

DNA (Fig. 3)[10]
DNA L-aTNA N-Cyanoimidazole


2. L-aTNA 16-mer L-aTNA (Template) 8-mer L-aTNA (8A8B)8B
3’8A 1’8A 3’
PAGE (Fig. 4)
Figure 2.
19
DNA ( 27%) L-aTNA (74%)
N-Cyanoimidazole
L-aTNA DNA
DNA

N-Cyanoimidazole

DNA 2
DNA 1
L-aTNA
2
Figure 4. L-aTNA () () Reaction conditions: 4oC, 12 h, [oligomer] = 1.0 μM, 20 mM N-Cyanoimidazole, 20 mM ZnCl2, 100 mM NaCl, Denaturing PAGE: 15% AA, 8 M Urea, 1.5 h, 750 V.
Figure 5.
Reaction conditions: 25oC, [oligomer] = 1.0 μM, 10 mM N- Cyanoimidazole, 20 mM MnCl2, 100 mM NaCl.
Newsletter-- Vol.34, No.2 (2019. 12)
20
L-aTNA

L-aTNA (Fig. 6)
PCR
L-aTNA
8- mer 5-mer, 4-mer, 3-mer, 2- mer

(Fig. 7)6h 5- mer 4-mer
24h 3-mer
DNA
Figure 7. L-aTNA
Reaction conditions: 4oC, [8A] = [Template] = 1.0 μM, [5B] = [4B] = [3B] = [2B] = 10 μM, 10 mM N-Cyanoimidazole, 20 mM MnCl2, 100 mM NaCl.
Figure 6. L-aTNA
Newsletter-- Vol.34, No.2 (2019. 12)
21
(Fig. 8) 12-mer
16-mer
12h 84% A
L- aTNA

L-aTNA DNA

L-aTNA SELEX XNA
XNA Prebiotic world ”XNA world”

Figure 8.
Reaction conditions: 4oC, [8A] = [Template] = 1.0 μM, [4B] = [4B’] = 10 μM, 10 mM N-Cyanoimidazole, 20 mM MnCl2, 100 mM NaCl.
Newsletter-- Vol.34, No.2 (2019. 12)
22
[1] (a) Obika, S.; Nanbu, D.; Hari, Y.; Andoh, J.; Morio, K.; Doi, T.; Imanishi, T. Tetrahedron Lett. 1998, 39, 5401.;
(b) Singh, S. K.; Nielsen, P.; Koshkin, A. A.; Wengel, J. Chem. Commun. 1998, 455 [2] Campbell, M. A.; Wengel, J. Chem. Soc. Rev. 2011, 40, 5680. [3] Schneider, K. C.; Benner, S. A. J. Am. Chem. Soc. 1990, 112, 453. [4] Zhang, L. L.; Peritz, A.; Meggers, E. J. Am. Chem. Soc. 2005, 127, 4174. [5] Asanuma, H.; Toda, T.; Murayama, K.; Liang, X.; Kashida, H. J. Am. Chem. Soc. 2010, 132, 14702. [6] Murayama, K.; Kashida, H.; Asanuma, H. Chem. Commun. 2015, 51, 6500. [7] Kashida, H.; Murayama, K.; Toda, T.; Asanuma, H. Angew. Chem., Int. Ed. 2011, 50, 1285. [8] Pinheiro, V. B.; Taylor, A. I.; Cozens, C.; Abramov, M.; Renders, M.; Zhang, S.; Chaput, J. C.; Wengel, J.;
Peak-Chew, S-Y.; McLaughlin, S. H.; Herdewijn, P.; Holliger, P. Science 2012, 336, 341. [9] Silverman, A. P.; Kool E. T. Chem. Rev. 2006, 106, 3775. [10] Kanaya, E.; Yanagawa, H. Biochemistry 1986, 25, 7423.
Newsletter-- Vol.34, No.2 (2019. 12)
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PPI PPI


1990


NSA 1a[4]
φ, ψ, ωφψ 1,3-

Newsletter-- Vol.34, No.2 (2019. 12)
24
N N

2006 Arvidsson [6] N

NSA
NSA MD
NSA 500
0.8
1.6
NSA

NSA DEER
NSA
NSA

NSA (a)
(b) NSA φψ(c) NSA

25
1HCOSYHMQCHMBC NMR
NOESY

4. NSA PPI NSA
NSA N

PPI MDM2 p53
MDM2 p53
p53 C transactivation domainTAD
p53-TAD Phe19Trp23Leu26 a[7]

NSA N p53-TAD
b1 N
NSA
c
NSA KD = 1.1 µM MDM2

NSA MDM2 p53-TAD
Ki = 0.93 µM MDM2 p53-TAD
NSA
MDM2 NSG
DEER NSA NSG
Tikhonov
26
NSG MDM2 NSA MDM2
PPI
PPI
PPI [8] Kodadek Lim
[9,10]


D2
MDM2-p53 NSA PPI (a) p53-TAD MDM2 (b)
p53-TAD NSA p53 F19W23
L26 αβ NSA Nα (c) p53
NSA MDM2-p53

27


CREST [1] Simon, R. J.; Kania, R. S.; Zuckermann, R. N.; Huebner, V. D.; Jewell, D. A.; Banville, S.; Ng, S.; Wang, L.;
Rosenberg, S.; Marlowe, C. K.; Spellmeyer, D. C.; Tan, R.; Frankel, A. D.; Santi, D. V.; Cohen, F. E.; Bartlett, P. A. Proc. Natl. Acad. Sci. U. S. A. 1992, 89, 9367−9371.
[2] Yu, P.; Liu, B.; Kodadek, T. Nat. Biotechnol. 2005, 23, 746−751. [3] Kodadek, T.; McEnaney, P. J. Chem. Commun. 2016, 52, 6038–6059. [4] Gao, Y.; Kodadek, T. Chem. Biol. 2013, 20, 360–369. [5] Morimoto, J.; Fukuda,Y.; Kuroda, D.; Watanabe, T.; Yoshida, F.; Asada, M.; Nakamura, T.; Senoo, A.;
Nagatoishi, S.; Tsumoto, K.; Sando, S. J. Am. Chem. Soc., 2019, 141, 14612−14623. [6] Zhang, S.; Prabpai, S.; Kongsaereeb, P.; Arvidsson, P. I. Chem. Commun. 2006, 497–499. [7] Kussie, P. H.; Gorina, S.; Marechal, V.; Elenbaas, B.; Moreau, J.; Levine, A. J.; Pavletich, N. P. Science 1996,
274, 948−953. [8] Shneider, J. A.; Craven, T. W.; Kasper, A. C.; Yun, C.; Haugbro, Briggs, E. M.; Svetlov, V.; Nudler, E.; Knaut,
H.; Bonneau, R.; Carabedian, M. J.; Kirshenbaum, K. Logan, S. K. Nat. Commun. 2018, 9, 4396. [9] Trader, D. J.; Simanski, S.; Kodadek, T. J. Am. Chem. Soc. 2015, 137, 6312–6319. [10] Oh, M.; Lee. J. H.; Moon, H.; Hyun, Y. J.; Lim, H. S. Angew. Chem. Int. Ed. 2016, 55, 602–606.
Newsletter-- Vol.34, No.2 (2019. 12)
28
P-
-
2
PPI
P-
S-S
20
29
2P-
()Y140 (
)()

X
X X
(Fig. 3) PPI
PPI
P-


JSPS [1] Kudo, S.; Caaveiro, M. M. J.; Tsumoto, K. Structure, 2016, 24, 1523. [2] Senoo, A.; Nagatoishi, S.; Moberg, A.; Babol, N. L.; Mitani, T.; Tashima, T.; Kudo, S.; Tsumoto, K. Chem. Commun., 2018, 54, 5350. [3] Kudo, S.; Caaveiro, M. M. J.; Nagatoishi, S.; Miyafusa, T.; Matsuura T.; Sudou Y.; Tsumoto K. Sci. Rep., 2017, 7, 39518
Newsletter-- Vol.34, No.2 (2019. 12)
30






31

SELEX FGFR2
DNA
FGFR2 A
FGFR2
FGFR2 2.




[1] Sarabipour and Hristoba. Nat. Commun. 2016, 4:7, 10262. [2] Ueki et al., Angew. Chem. Int. Ed., 2016, 55, 579. [3] Ueki et al., J. Am. Chem. Soc. 2017, 139, 6554.
. Aptamer
32
photoSLIPT
1 2JST
1990



1.

CFPGFPYFP mCherry

SLIPT


a
b
33
eDHFR TMP
o-(NVOC)
NVOC CFPGFP

(PIP3)PIP3
PIP3
PI3K mDcTMPNVOC
( 2a)PI3K p110 iSH2 eDHFR
(eDHFR-Venus-iSH2)eDHFR-Venus-iSH2 iSH2
eDHFR-Venus-iSH2 mDcTMPNVOC
3
( 2b)photoSLIPT


[1] Ishida, M.; Watanabe, H.; Takigawa, K.; Kurishita, Y.; Oki, C.; Nakamura, A.; Hamachi, I.; Tsukiji, S. J. Am.
Chem. Soc. 2013, 135, 12684. [2] Nakamura, A.; Katahira, R.; Sawada, S.; Shinoda, E.; Kuwata, K.; Yoshii, T.; Tsukiji, S. Biochemistry. in press [3] Nakamura, A.; Oki, C.; Kato, K.; Fujinuma, S.; Maryu, G.; Kuwata, K.; Yoshii, T.; Matsuda, M.; Aoki, K.;
Tsukiji, S. ChemRxiv, DOI: 10.26434/chemrxiv.8222456
a
b
34
RNA
4



RNA G- quadruplex 1)G-quadruplex

G-quadruplex
RT 3)RNA
cDNA
G-quadruplex Fig. 2
RNA Staple DNA
Fig. 1. Staple mRNA RNA G-quadruplex
Newsletter-- Vol.34, No.2 (2019. 12)
35
RNA G-quadruplex
TPM3 5’UTR
Firefly luciferaseFluc mRNA
Staple
Staple G-quadruplex
TPM3 Staple



4. Staple mRNA G-quadruplex


Staple Staple
RNAi


[1] Kumari, S.; Bugaut, A.; Huppert, J. L.; Balasubramanian, S. Nat. Chem. Biol. 2007, 3, 218–221 [2] Xu, S.; Li, Q.; Xiang, J.; Yang, Q.; Sun, H.; Guan, A.; Wang, L.; Liu, Y.; Yu, L.; Shi, Y.; Chen, H.; Tang, Y. Sci.
Rep. 2016, 6, 24793. [3] Hagihara, M.; Yoneda, K.; Yabuuchi, H.; Okuno, Y.; Nakatani, K. Bioorg. Med. Chem. Lett., 2010, 20, 2350-
2353.
Fig. 2. RT
36
1
1 1 2 3 1 4 4 5 6 7 3,
8 1, 9, 10
123456
789 10AMED-CREST


37
[2]

alkaline
phosphatases (ALPs)
ALPTNAP
Fig.3
ectonucleotide
pyrophosphatases/phosphodiesterases (ENPPs)

(Fig 5)
[1] R.Watanabe et al., Nat. Commun, 2014, 5, 4519. [2] S.Sakamoto et al., Sci. Adv, in press
Fig 4. AENPP
B

A
B

38
NMDA
………

(NMDAR)AMPA (AMPAR)
AMPAR



NMDAR NMDAR
NMDAR
39
NMDA




[1] Fujishima, S. et al. J. Am. Chem. Soc., 2012, 134, 3961. [2] Wakayama, S. et al. Nat. Commun., 2017, 8,14850
2(a)
(b) 2
LDAI (0h)
LDAI()
40
1 2
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41
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[1] Beck, A.; Goetsch, L.; Dumontet, C.; Corvaïa, N. Nat. Publ. Gr. 2017, 16 (5), 315.
[2] Yamada, K.; Ito, Y. ChemBioChem 2019, 20, 2729.
[3] Sato, S.; Hatano, K.; Tsushima, M.; Nakamura, H. Chem. Commun. 2018, 54 (46), 5871.
[4] Li, R.; Dowd, V.; Stewart, D. J.; Burton, S. J.; Lowe, C. R. Nat. Biotechnol. 1998, 16, 190.
[5] Tsushima, M.; Sato, S.; Niwa, T.; Taguchi, H.; Nakamura, H. Chem. Commun. 2019, 55, 13275.
Figure 2. Fc
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[1] Urano, Y. et al. Science Transl Med, 3, 110 (2011). [2] Ueo, H. et al. Sci. Rep., 5, 12080 (2015). [3] Asanuma,
D. et al. Nat. Commun., 6, 6463 (2015). [4] Komatsu, T. et al. J. Am. Chem. Soc., 135, 6002-6005 (2013).
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(Q)

45

D-aTNA
aTNA
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Q1
Q3 Cy3
FAM
9
(Fig.5)
[1] H. Asanuma, et al., J. Am. Chem. Soc., 2010, 132, 14702-14703. [2] K. Murayama, et al., ChemBioChem, 2015, 16, 1298-1301.
Fig. 2. DNA D-aTNA
Fig. 3
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