研究業績・活動報告2019

概要

東北大学
多元物質科学研究所
研 究 業 績・活 動 報 告
2019 年 (令和元年)12 月

多元物質科学研究所

研究業績・活動報告
目 次
研究活動報告 ·········································································
有機・生命科学研究部門 ···································································································

1
1

無機材料研究部門 ············································································································ 15
プロセスシステム工学研究部門 ·························································································· 28
計測研究部門 ·················································································································· 40
非鉄金属製錬環境科学研究部門 ·························································································· 59
放射光次世代計測科学連携研究部門 ···················································································· 61
金属資源プロセス研究センター ·························································································· 62
先端計測開発センター ······································································································ 81
高分子・ハイブリッド材料研究センター ·············································································· 89
新機能無機物質探索研究センター ······················································································· 103

研究会報告 ············································································ 114
学会発表講演目録 ··································································· 138
有機・生命科学研究部門 ··································································································· 138
無機材料研究部門 ············································································································ 139
プロセスシステム工学研究部門 ·························································································· 141
計測研究部門 ·················································································································· 143
非鉄金属製錬環境科学研究部門 ·························································································· 145
金属資源プロセス研究センター ·························································································· 145
先端計測開発センター ······································································································ 148
高分子・ハイブリッド材料研究センター ·············································································· 149
新機能無機物質探索研究センター ······················································································· 151

研究業績目録 ········································································· 153
有機・生命科学研究部門 ··································································································· 153
無機材料研究部門 ············································································································ 156
プロセスシステム工学研究部門 ·························································································· 159
計測研究部門 ·················································································································· 162
非鉄金属製錬環境科学研究部門 ·························································································· 169
金属資源プロセス研究センター ·························································································· 169
先端計測開発センター ······································································································ 175
高分子・ハイブリッド材料研究センター ·············································································· 177
新機能無機物質探索研究センター ······················································································· 183

業績目録著者索引 ··································································· 187

研究活動報告

1

⏕࿨ᶵ⬟ศᏊྜᡂ໬Ꮫ◊✲ศ㔝

࠙◊✲άືሗ࿌ࠚ

㸦2019. 1㹼2019. 12㸧

ᩍ   ᤵ 㸸Ọḟ ྐ
ຓ   ᩍ 㸸㨣ሯ࿴ගࠊᒸᮧ⚽⣖
஦ົ⿵బဨ㸸ᮌᮧ⌮㤶
኱ Ꮫ 㝔 ⏕ 㸸ᯇᒣ₶Ⅸ(㹼2019ᖺ3᭶)ࠊ⚟㛫Ύ஀(㹼2019ᖺ3᭶)ࠊᑠᔱ࠿ࢇ࡞(㹼2019ᖺ3᭶)ࠊ
బ⸨⨾ဏ(㹼2019ᖺ3᭶)ࠊ▼⏣ ᆂ(㹼2019ᖺ3᭶)ࠊ࣭ࣞࢺ࢔࣭࣮ࣥ࢝ࣥ
(㹼2019ᖺ3᭶)ࠊ▼ᕝಇஓࠊఀ⸨㔛ዉ(2019ᖺ4᭶㹼)ࠊ▮ᓥࡉࡸ࠿(2019ᖺ4᭶㹼)ࠊ
ࢺ࣭࣭ࣜࣥ࣍ࣥࢪࣕࣥ(2019ᖺ9᭶㹼)ࠊ၈ь᮶(2019ᖺ9᭶㹼)ࠊ䱸 㞵᱒
(2019ᖺ9᭶㹼)
Ꮫ 㒊 ⏕㸸࢞ࣥ࣎ࣝࢺ࣭࢚ࣝࢸ࢕ࢫ(2019ᖺ7᭶㹼)
◊ ✲ ⏕㸸ⴷ ༟᫈(2019ᖺ10᭶㹼)

ᮏ◊✲ศ㔝࡛ࡣࠊ᭷ᶵ໬Ꮫࢆ࣮࣋ࢫ࡟ᶵ⬟ᛶศᏊࢆタィ࣭ྜᡂࡋࠊࡑࢀࡽࢆ⏝࠸࡚㑇ఏᏊⓎ⌧ࢆ໬
Ꮫⓗ࡟ไᚚࡍࡿ᪉ἲㄽࡢ㛤Ⓨࢆ┠ᣦࡋ࡚◊✲άືࢆ⾜ࡗ࡚࠸ࡿࠋ2019ᖺࡢᮏ◊✲ᡤ࡟࠾ࡅࡿ୺࡞◊✲
άື࡜ࡋ࡚ࡣࠊ௨ୗࡢࡼ࠺࡟ᴫᣓࡉࢀࡿࠋ
 ᰾㓟㧗ḟᵓ㐀ࢆ࢔ࣝ࢟ࣝ໬ࡍࡿ2))21ᆺ཯ᛂᛶศᏊࡢ㛤Ⓨ1)
㏆ᖺࠊ᰾㓟ࡀᙧᡂࡍࡿ㧗ḟᵓ㐀ࡣ㑇ఏᏊⓎ⌧ไᚚᶵᵓ࡟࠾࠸࡚㔜せ࡞ᙺ๭ࢆᣢࡘࡇ࡜ࡀศ࠿ࡗ࡚ࡁ
࡚࠸ࡿࠋࡇࢀࡽࡢ㧗ḟᵓ㐀ࡣ⺮ⓑ㉁࡜ࡢ┦஫స⏝㒊఩࡟࡞ࡿࡇ࡜ࡀከࡃࠊࡇࡢ┦஫స⏝ࢆຠ⋡ⓗ࡟㜼
ᐖࡍࡿ࡟ࡣᶆⓗ㧗ḟᵓ㐀࡟ᑐࡋ࡚ඹ᭷⤖ྜࢆᙧᡂࡍࡿศᏊࡢ㛤Ⓨࡀᚲせ࡛࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋᡃࠎࡢ
◊✲ᐊ࡛ࡣ᪤࡟ࠊ᰾㓟ࡢ㧗ḟᵓ㐀࡜ࡋ࡚ࠊG4ᵓ㐀ཬࡧT-T࣑ࢫ࣐ࢵࢳᵓ㐀࡟ᑐࡋ࡚࢔ࣝ࢟ࣝ໬཯ᛂࡍࡿ
ศᏊࢆ㛤Ⓨࡋ࡚࠸ࡿ㸦ᅗ㸯㸧ࠋ
N
O

N

N

R

N

H
N

N
N

N H N

N

N H

NH2

H

H2 N

N
O

1

HN

O


ࢢ࢔ࢽࣥ㸲ᮏ㙐
*


O

O

NH

77࣑ࢫ࣐ࢵࢳ

N

H

O

O

NH

H

OMe

N

N



N

H
H

N
Cl

O

DNA N TN

N
N

H

N

N

N TN

DNA

O

N

2

Org. Biomol. Chem., 2018, 16, 1436

Nucl. Acids Res. 2018, 46, 1059

ᅗ㸯 㧗ḟᵓ㐀࡟ᑐࡍࡿ࢔ࣝ࢟ࣝ໬ࣉ࣮ࣟࣈ

ࡋ࠿ࡋࠊ࠸ࡎࢀࡶ཯ᛂࡀ㐜࠸ࡇ࡜ࡀࢃ࠿ࡗ࡚࠾ࡾࠊ㏿࠸཯ᛂ㏿ᗘࢆᣢࡘศᏊࡢ㛤Ⓨࡀᚲせ࡛࠶ࡿࠋ

཯ᛂ㏿ᗘࢆྥୖࡋࡓࣉ࣮ࣟࣈࡣࠊ௚ࡢ཯ᛂ✀࡟ᑐࡋ࡚ࡶ཯ᛂࡍࡿྍ⬟ᛶࡀ࠶ࡾࠊ⣽⬊ෆ࡟࠾ࡅࡿ࢔ࣝ
࢟ࣝ໬཯ᛂ࡟ࡣ㐺ᛂ࡛ࡁ࡞࠸ࠋࡑࡇ࡛ࠊࡇࢀࡽࡢࢪ࣐ࣞࣥࢆゎỴࡍࡿ᪉ἲ࡜ࡋ࡚ࠊOFF-ONᶵ⬟ࢆ௜୚
ࡋࡓ཯ᛂᛶࣉ࣮ࣟࣈ࡜ࡋ࡚ࠊࣅࢽࣝ࢟ࢼࢰࣜࣥㄏᑟయ(VQ)ࢆタィࡋࡓ㸦ᅗ㸰㸧ࠋᮏࣉ࣮ࣟࣈࡣᶆⓗࡢ
᰾㓟㧗ḟᵓ㐀࡟᥋㏆ࡋࠊ⬺㞳཯ᛂࡀㄏᑟࡉࢀ㧗࠸཯ᛂᛶࢆᣢࡘࣅࢽࣝᇶࡀㄏᑟࡉࢀࡿ࡜ᮇᚅࡋࡓࠋࡲ
ࡎࠊ⬺㞳ᇶ࡜ࡋ࡚ࢫࣝ࣍࢟ࢩࢻ㸦SOR㸧ࠊࢳ࢜ࣇ࢙ࢽࣝ㸦SPh㸧ࠊࢳ࣓࢜ࢳࣝ㸦SMe㸧ᇶࢆᣢࡘㄏᑟయ
ࢆྜᡂࡋࠊࡑࡢ཯ᛂᛶࢆ᳨ウࡋࡓࠋࡑࡢ⤖ᯝࠊG4DNA࡟ᑐࡍࡿ཯ᛂ㏿ᗘࡣSOR>SPh>SMeࡢ㡰࡛࠶ࡿ
ࡇ࡜ࡀࢃ࠿ࡗࡓࠋࡉࡽ࡟ࡍ࡭࡚ࡢᏳᐃ๓㥑యࡣࠊG4DNA࡟ᑐࡋ࡚ࡣ཯ᛂࡀ㐍⾜ࡋࡓࡢ࡟ᑐࡋࠊ୍ᮏ㙐
DNAࡸ஧ᮏ㙐DNA࡟ࡣ࡯࡜ࢇ࡝཯ᛂࡏࡎࠊG4DNA࡟ᑐࡍࡿ㧗࠸཯ᛂ㑅ᢥᛶࢆ♧ࡍࡇ࡜ࡀࢃ࠿ࡗࡓࠋࡉ

研究活動報告

2

ࡽ࡟཯ᛂ࣓࢝ࢽࢬ࣒ࢆ᳨ウࡋࡓ⤖ᯝࠊ⬺㞳ᇶ࡟ࡼࡗ࡚࢔ࣝ࢟ࣝ໬཯ᛂࡢ࣓࢝ࢽࢬ࣒ࡀ␗࡞ࡿࡇ࡜ࡀࢃ
࠿ࡗࡓ㸦ᅗ㸱㸧ࠋ
Target DNA
O

O

O
N

N

N

N

X

N

R

R

stable
OFF

-

VQ-S(O)Me

ON
S
O

S

R=

O

HN

H
N

N

άᛶ໬

SMe

R

VQ-SMe

ᖹ⾮཯ᛂ

S

R

SPh
O

R

S

X

N

S

SMe S(O)Me

N

X

N

G-4

O
N

X=

O

N

S(O)Me

R

Reactive

O

⮬Ⓨⓗ

N

-

VQ-SPh

O

X

G-4

N

S

G4

N
R

O
N

ᅗ㸰 2))21ᆺ࢔ࣝ࢟ࣝ໬ࣉ࣮ࣟࣈ

ᅗ㸱 2))21ᆺ࢔ࣝ࢟ࣝ໬ࡢ᥎ᐃ࣓࢝ࢽࢬ࣒

ࡲࡓVQ-SPhయG4ᵓ㐀ࡢࡳ࡛ࡣ࡞ࡃT-T࣑ࢫ࣐ࢵࢳᵓ㐀࡟ᑐࡋ࡚ࡶ࢔ࣝ࢟ࣝ໬ࡀ㐍⾜ࡍࡿࡇ࡜ࡀࢃ࠿
ࡗࡓࠋ⌧ᅾࠊR㒊఩࡟G4ᵓ㐀࡟㑅ᢥⓗ࡟⤖ྜࡍࡿศᏊࢆᑟධࡋࠊG4㑅ᢥⓗ࡞࢔ࣝ࢟ࣝ໬཯ᛂ࡟ࡘ࠸࡚
᳨ウ୰࡛࠶ࡿࠋ
 ᯫᶫ཯ᛂᛶࢆᣢࡘேᕤ᰾㓟ࡢ㛤Ⓨ
ᡃࠎࡢ◊✲ᐊ࡛ࡣࠊᶆⓗRNA୰ࡢࢳ࣑ࣥ࡟ᑐࡋ࡚㑅ᢥⓗ࡟ᯫᶫ཯ᛂࡍࡿ཯ᛂᛶศᏊ(3)ࢆ㛤Ⓨࡋ࡚࠾
ࡾࠊ᪤࡟ࡇࡢศᏊࢆྵࡴ࢜ࣜࢦ2´OMe RNAࡀࣔࢹࣝ⣽⬊ෆ࡟࠾࠸࡚miRNAࢆຠ⋡ⓗ࡟㜼ᐖࡍࡿࡇ࡜ࢆ
ሗ࿌ࡋ࡚࠸ࡿ㸦ChemBioChem, 2013, 14, 1427-1429㸧ࠋࡋ࠿ࡋࠊᯫᶫ཯ᛂᛶศᏊ(3)䛿ෆᅾᛶࡢRNAࢆ
ᶆⓗ࡜ࡋࡓຠ⋡ⓗ࡞㜼ᐖ࡟ࡣᡂຌࡋ࡚࠸࡞࠸ࠋࡑࡢ୍ᅉ࡜ࡋ࡚ࠊAVP (3)ࡢ཯ᛂ㏿ᗘࡀ㐜࠸ࡇ࡜ࡀ(~20
h)⪃࠼ࡽࢀࡿࠋࡑࡇ࡛ࠊ཯ᛂ㏿ᗘࡢྥୖࢆ┠ᣦࡋ7-ࢹ࢔ࢨࢢ࢔ࢽࣥࡢࣅࢽࣝㄏᑟయ(4)ࢆタィࡋࠊ4ࢆ⤌
ࡳ㎸ࢇࡔ࢜ࣜࢦ2´OMe RNAࢆྜᡂࡋࡓࡇࢁࠊᶆⓗRNAࡢ࢘ࣜࢪࣥ࡟ᑐࡋ࡚཯ᛂ30ศ௨ෆ࡟⣙80㸣ࡢ཰
⋡࡛཯ᛂࡍࡿࡇ࡜ࡀࢃ࠿ࡗࡓ2)ࠋࡋ࠿ࡋࠊᮏศᏊࡢྜᡂࡣ㠀ᖖ࡟࣮ࣝࢺࡀ㛗࠸ࡓࡵࠊࡼࡾྜᡂ࣮ࣝࢺࡀ
▷࠸ㄏᑟయ࡜ࡋ࡚ࠊ㠀⎔≧ᆺࡢศᏊ(5)ࢆタィࡋࡓࠊᮏศᏊࡣ6ࢫࢸࢵࣉ࡛࢜ࣜࢦ๓㥑యࡀྜᡂ࡛ࡁࡿࡇ
࡜ࠊࡉࡽ࡟㠀⎔≧᰾㓟SNAࡣᏳᐃ࡞ேᕤ᰾㓟࡜ࡋ࡚ᒎ㛤࡛ࡁࡿࡇ࡜࠿ࡽ⣽⬊ෆ࡟ᛂ⏝ྍ⬟࡛࠶ࡿ࡜⪃
࠼ࡽࢀࡿࠋᮏศᏊࢆ⤌ࡳ㎸ࢇࡔ࢜ࣜࢦ2´OMe RNAࢆྜᡂࡋࠊ཯ᛂᛶࢆ᳨ウࡋࡓ࡜ࡇࢁࠊ4ࡼࡾ཯ᛂ㏿
ᗘࡀ㐜࠸ࡶࡢࡢࠊAVP (3)䛻ẚ㍑䛩䜛䛸䛛䛺䜚᪩䛔཯ᛂ㏿ᗘ䛷཯ᛂ䛩䜛䛣䛸䛜䜟䛛䛳䛯䚹⌧ᅾ䚸5ࢆ⤌ࡳ㎸ࢇ
ࡔ࢜ࣜࢦSNAࡢྜᡂࢆ᳨ウ୰࡛࠶ࡿࠋ
O
N
N

O
O
O

N

N

O

H N

N H
H

)
NA

N
t

O

ge
ar

(T

N

R

N

O
O

N

NH2

OMe

3

O

OMe

N

O
O
O

OMe

N

N

4

SMe

H N

N H
H

O

N

A)

N
t

ge

ar
(T

RN

O

N

H
N
O

N

NH2

O

5

ᅗ㸲 ᚑ᮶ࡢᯫᶫ཯ᛂᛶ᰾㓟࡜㓄ᗙᅛᐃ໬࡟ࡼࡾ཯ᛂᛶྥୖࢆᮇᚅࡋࡓ཯ᛂᛶ᰾㓟

1) Onizuka, K., Hasemi, E.M., Sato, N., Tsuji, G., Ishikawa, S., Ozawa, M., Tanno, K., Yamada, K., Nagatsugi
F., Nucl. Acids Res., 47, 6578–6589 (2019)
2) Yamada, K., Abe, Y., Murase, H., Ida, Y., Hagihara, S., Nagatsugi, F., J. Org. Chem., 83, 8851-8862(2018)

◊㻌 ✲㻌 ά㻌 ື㻌 ሗ㻌 ࿌

研究活動報告

3

࠙◊✲άືሗ࿌ࠚ㻌 㻌

⏕࿨ᶵ⬟ไᚚ≀㉁໬Ꮫ◊✲ศ㔝䠄2019䠊1䡚2019䠊12䠅㻌

ᩍ
ᤵ 㻦㻌 ࿴⏣㻌 ೺ᙪ㻌
෸ ᩍ ᤵ 㻦㻌 Ⲩᮌ㻌 ಖᖾ㻘㻌 ຓ㻌 㻌 ᩍ㻌 䠖㻌 すᔱ㻌 ᨻᶞ㻌
༤ኈ◊✲ဨ㻌 㻦㻌 㻌✄ᇉ㻌 㞞ோ㻌
኱ Ꮫ 㝔 ⏕ 㻌 㻦㻌㼃㼕㼖㼍㼗㻌㼅㻻㻿㻼㻭㻺㼅㻭㻘㻌 㝞㻌 ☐ᾏ㻘㻌 ኱➉㻌 ೺ኴ㻘㻌 ᰠᓮ㻌 ▱඾㻘㻌
Ἑྜ ⨾ဏ㻘㻌 ⛬㻌 ᒾ㻘㻌 ▼⃝㻌 ㄔஓ㻘㻌 ᯇᶫ㻌 ⏤ె㻘㻌 ▮㔝㻌 ㍤㻌
Ꮫ 㒊 ⏕㻌 㻦㻌 㻼㼍㼚㼐㼑㼥㻌㻿㻭㻰㻵㻷㻿㻴㼅㻭
㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
ᮏ◊✲ศ㔝䛷䛿䚸䛜䜣⣽⬊㑅ᢥⓗ᰾㓟་⸆䛾㛤Ⓨ䜔䝍䞁䝟䜽㉁䛜᭷䛩䜛⤖ྜ䝃䜲䝖䜢䜻䝷䝹䝘䝜䝸䜰䜽䝍䞊
䛸䛧䛶ά⏝䛧䛯㉸ศᏊ୙ᩧග཯ᛂ⣔䛾ᵓ⠏䛺䛹䚸᰾㓟䜔䝍䞁䝟䜽㉁䛺䛹⏕య㧗ศᏊ䛾ḟୡ௦䜲䞁䝔䝸䝆䜵䞁䝖
ᆺ䝘䝜䝞䜲䜸ᶵ⬟ᮦᩱ䜈䛾ᛂ⏝ᒎ㛤䛻ྲྀ䜚⤌䜣䛷䛔䜛䚸䛥䜙䛻⏕యศᏊ䛾ᵓ㐀ኚ໬䛸ᶵ⬟ไᚚᶵᵓゎ᫂䜢┠
ᣦ䛧䛯䚸㧗ឤᗘ䞉㧗᫬㛫ศゎ෇஧Ⰽ䝇䝨䜽䝖䝹 ᐃ⿦⨨㛤Ⓨ䛻䜒ྲྀ䜚⤌䜏䚸⏕࿨໬Ꮫ䛛䜙≀⌮໬Ꮫ䜎䛷ศ㔝
ᶓ᩿ⓗ䛻ᇶ♏䛛䜙ᛂ⏝䜎䛷ᖜᗈ䛔◊✲άື䜢ᒎ㛤䛧䛶䛔䜛䚹2019 ᖺ䛾◊✲άື䛿䚸௨ୗ䛾䜘䛖䛻ᴫᣓ䛥䜜
䜛䚹
㻌
䠍䠊㻌 䝚䜽䝺䜰䞊䝊άᛶྥୖ䜢ᣦྥ䛧䛯 㻰㻺㻭㻙ேᕤ᰾㓟䜻䝯䝷ศᏊᵓ㐀タィ䛸᪂ᶵ⬟๰〇㻌
㏆ᖺࠊḟୡ௦ࡢศᏊᶆⓗ་⸆࡜ࡋ࡚ὀ┠ࡉࢀ࡚࠸ࡿ᰾㓟་⸆ࡀ᭷ຠ࡟⸆ຠⓎ⌧ࡍࡿࡓࡵ࡟ࡣࠊ㸯㸧
㧗࠸⏕యෆᏳᐃᛶࠊ㸰㸧ᶆⓗ᰾㓟࡬ࡢ㧗࠸≉␗ᛶ࡜」ྜయᏳᐃᛶࡀồࡵࡽࢀࠊኳ↛ᆺ DNA/RNA ࡟໬
Ꮫಟ㣭ࢆ᪋ࡋࡓಟ㣭᰾㓟/ேᕤ᰾㓟ࡢ㛤Ⓨࡀ⢭ຊⓗ࡟◊✲ࡉࢀ࡚࠸ࡿࠋࡇࢀࡲ࡛ඃࢀࡓಟ㣭/ ேᕤ᰾㓟
ࡀሗ࿌ࡉࢀ࡚࠸ࡿࡶࡢࡢࠊᶆⓗ᰾㓟࡜㢮ఝ㓄ิࢆ᭷ࡍࡿ㠀ᶆⓗ᰾㓟࡬ࡢ⤖ྜ࡟㉳ᅉࡍࡿ࢜ࣇࢱ࣮ࢤࢵ
ࢺຠᯝࠊᶆⓗ᰾㓟ㄆ㆑࡟౫Ꮡࡋ࡞࠸᰾㓟་⸆≉᭷ࡢẘᛶ㸦ᗈ⩏ࡢ࢜ࣇࢱ࣮ࢤࢵࢺຠᯝ㸧ࡢⓎ⌧ࡀᐇ⏝
໬࡟ྥࡅ࡚ゎỴࡍ࡭ࡁㄢ㢟࡜ࡋ࡚ᣦ᦬ࡉࢀ࡚࠸ࡿࠋᮏ◊✲࡛ࡣࠊ᰾㓟་⸆≉᭷ࡢㄢ㢟ࢆゎỴࡋᚓࡿ᪉
ἲㄽ࡜ࡋ࡚ࠊ”ゐ፹ⓗ᰾㓟་⸆”ࢆᥦ᱌ࡋࠊ᪂つศᏊ⣔ᵓ⠏࡟ྲྀࡾ⤌ࢇࡔࠋ
ᗈ⩏ࡢ࢜ࣇࢱ࣮ࢤࢵࢺຠᯝࡢඞ᭹࡬ྥࡅࡓ᪉ἲㄽ࡜ࡋ࡚ࠊ᰾㓟་⸆ࡢᢞ୚㔞ࡢపῶࡀᥦ᱌ࡉࢀ࡚࠸
ࡿࠋࡋ࠿ࡋࠊ⣽⬊ෆᑟධ㔞ࡀ sub-nM ࣞ࣋ࣝࡀ㝈⏺࡜ሗ࿌ࡉࢀ࡚࠸ࡿ࢔ࣥࢳࢭࣥࢫ᰾㓟㸦ASO㸧ศᏊࢆ
⏝࠸࡚ࠊⓎ⌧㔞ࡀ sub-µM ࣞ࣋ࣝࡢ mRNA ࢆᶆⓗ࡜ࡍࡿ⣔࡛ࡣࡶࡕࢁࢇࠊnM–pM ࣞ࣋ࣝࡢ⣽⬊ෆⓎ⌧
㔞࡛ᶵ⬟ࢆⓎ᥹ࡍࡿ miRNA ࢆᶆⓗ࡜ࡍࡿ⣔࡛ࡶࣇ࢕࣮ࢻࣂࢵࢡᶵᵓࡀሗ࿌ࡉࢀࠊᶆⓗ RNA ࡜ ASO ࡢ
1:1 」ྜయᙧᡂ࡟ᇶ࡙ࡃ⸆ຠⓎ⌧ᡓ␎࡛ࡣࠊ༑ศ࡞἞⒪ຠᯝࡀᮇᚅฟ᮶࡞࠸ࡇ࡜ࡀᣦ᦬ࡉࢀ࡚࠸ࡿࠋᮏ
ㄢ㢟ࡢゎỴἲ࡜ࡋ࡚ࠊᑡ㔞ࡢ ASO ࡛ᶆⓗ RNA ࢆゐ፹ⓗ࡟ษ᩿ࡍࡿ RNaseH ࢆά⏝ࡋࡓゐ፹ⓗ᰾㓟་
⸆ἲࡀὀ┠ࡉࢀ࡚࠸ࡿࠋᮏ◊✲࡛ࡣຠ⋡ⓗ࡞ゐ፹ⓗ᰾㓟་⸆⣔ᵓ⠏ࢆ┠ᣦࡋࠊDNA ࡜ேᕤ᰾㓟ࢆ⼥ྜ
ࡋࡓ᪂つศᏊ⣔ࡢᵓ⠏࡜ᐇドᐇ㦂࡟ྲྀࡾ⤌ࢇࡔࠋ
RNase H ࡣ DNA•RNA ஧㔜㙐ࢆㄆ㆑ࡋࠊRNA 㙐ࡢࡳࢆษ᩿ࡍࡿ
㓝⣲࡛࠶ࡿࠋ㧗ຠ⋡࡞ゐ፹ⓗ ASO ⣔ᵓ⠏࡟ࡣࠊRNaseH ࡟ࡼࡿᶆⓗ
RNA ࡢษ᩿ຠ⋡ྥୖࡢࡳ࡞ࡽࡎࠊ௦ㅰᅇ㌿ᩘࡢቑຍࡀ᭷ຠ࡜ᮇᚅ
ࡉࢀࡿࠋࡇࡢほⅬ࠿ࡽࠊRNA ษ᩿ᚋࡢゎ㞳㐣⛬࡟╔┠ࡋࠊษ᩿ᚋ
ᶆⓗ RNA ࡢ」ྜయ࠿ࡽ㎿㏿ゎ㞳ࢆᐇ⌧ࡍࢀࡤࠊ௦ㅰᅇ㌿ᩘࡢቑຍ
ࡀᮇᚅࡉࢀࡿࠋゎ㞳ຠ⋡ྥୖࢆᐇ⌧ࡍࡿࡓࡵ࡟ࡣࠊษ᩿ᚋ RNA ᩿
∦࡜ ASO ࡜ࡢ」ྜయᏳᐃᛶ࡟╔┠ࡋࠊษ᩿ᚋࡢ」ྜయᏳᐃᛶࡀ⏕ Fig. 1. Structure of chimera:RNA duplex
with RNase H.

◊㻌 ✲㻌 ά㻌 ື㻌 ሗ㻌 ࿌

研究活動報告

యෆ⎔ቃ 37 ºC ௨ୗࡢ Tm ࡜࡞ࡿࡼ࠺࡞఩⨨࡛ࡢ㑅ᢥⓗ୍⟠ᡤษ᩿ࡀ㔜せ࡛࠶ࡿ࡜Ⓨ᱌ࡋࡓࠋ㑅ᢥⓗ୍
⟠ᡤษ᩿ࢆ㐩ᡂࡍࡿࡓࡵ࡟ࠊRNaseH-DNA•RNA 」ྜయࡢ X ⥺⤖ᬗᵓ㐀ࢆヲ⣽࡟⪃ᐹࡋࡓࠋᮏ⤖ᬗᵓ㐀
ࡼࡾࠊRNase H ษ᩿άᛶࢧ࢖ࢺࡢୗὶഃ࡟ࠊሷᇶᛶ࢔࣑ࣀ㓟ṧᇶ࠿ࡽᵓᡂࡉࢀࡿ DNA ⤖ྜࢳࣕࢿࣝࡀ
Ꮡᅾࡋࠊࡇࡢ⤖ྜࢳࣕࢿࣝࡀࣜࣥ㓟㦵᱁㈇㟁Ⲵࢆ≉␗ⓗ࡟ㄆ㆑ࡍࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋࡑࡢ⤖ᯝ
࡜ࡋ࡚ࠊRNA 㙐ഃࡣࣇࣜࢵࣉ࢔࢘ࢺࡋࠊRNase H ࡢάᛶࢧ࢖ࢺ࡬ᘬࡁ㎸ࡲࢀࡿࠋDNA ⤖ྜࢳࣕࢿࣝࡣ
DNA•RNA ஧㔜㙐ࡢ 5–6 ሷᇶᑐ㛗࡟┦ᙜࡍࡿࢧ࢖ࢬ࡜࡞ࡗ࡚࠸ࡿࡓࡵࠊDNA ⤖ྜ఩⨨ࢆไᚚ࡛ࡁࢀࡤࠊ
RNA ⤖ྜ఩⨨ࡶᚲ↛ⓗ࡟Ỵࡲࡗ࡚ࡃࡿ࡜⪃࠼ࡽࢀࡿࠋࡇࡢࡼ࠺࡞▱ぢ࡟ᇶ࡙ࡁࠊ࢔ࢽ࢜ࣥᛶ⢾-ࣜࣥ㓟
㦵᱁ࢆ᭷ࡍࡿ DNA ࡜㟁Ⲵࢆᣢࡓ࡞࠸࢔࣑ࢻ㦵᱁࠿ࡽ࡞ࡿேᕤ᰾㓟㸦PNA/PRNA㸧ࢆ⼥ྜࡋࡓ࣓࢟ࣛศ
Ꮚࢆ㐺ษ࡟タィࡍࡿࡇ࡜࡟ࡼࡾࠊᶆⓗ RNA ࡢ PNA-DNA ࢪࣕࣥࢡࢩࣙࣥ㒊఩㏆ഐ࡟࠾ࡅࡿ㑅ᢥⓗ୍⟠
ᡤ RNA ษ᩿ࢆᐇ⌧࡛ࡁࡿ࡜⪃࠼ࡓ㸦Fig.1㸧
ࠋᐇ㝿࡟タィࡋࡓ DNA-PNA/PRNA ࣓࢟ࣛศᏊࢆ DNA ⮬ື
ྜᡂ࠾ࡼࡧ Fmoc ࣌ࣉࢳࢻᅛ┦ྜᡂἲ࡟ࡼࡾྜᡂࡋࠊDNA-PNA/PRNA ࣓࢟ࣛศᏊࡢ RNase H ࡟ࡼࡿ
RNA ษ᩿άᛶࢆࢤࣝ㟁ẼὋື࡟ࡼࡾゎᯒࡋࡓ⤖ᯝࠊ
ኳ↛ᆺ DNA ࡢሙྜ࡟ࡣ㠀≉␗ⓗ࡞ษ᩿ࡀ㉳ࡇࡾࠊ
ᵝࠎ࡞㛗ࡉࡢ RNA ᩿∦ࡀぢࡽࢀࡓࡢ࡟ᑐࡋ࡚ࠊ࣓࢟ࣛศᏊࡢሙྜ࡟ࡣࠊண᝿㏻ࡾ DNA-PNA ࢪࣕࣥࢡ
ࢩࣙࣥ㒊఩࡟࠾࠸࡚㑅ᢥⓗ࡞ RNA ษ᩿ࡀほ ࡉࢀࡓࠋ
௨ୖ䚸ᮏᖺ䛾◊✲䛛䜙䚸DNA 䛸 PRNA 䜢⼥ྜ䛧䛯䜻䝯䝷ேᕤ᰾㓟(PRNA)䛿䚸䝚䜽䝺䜰䞊䝊䛾ᶆⓗ RNA 䛾ษ᩿
άᛶ䜢኱ᖜ䛻ྥୖฟ᮶䜛䛣䛸䜢᫂䜙䛛䛸䛧䚸ᮾ໭኱Ꮫ䛛䜙≉チ⏦ㄳ䛥䜜䚸BIP ⫱ᡂ䝥䝻䝆䜵䜽䝖䛻᥇ᢥ䛥䜜䛯䚹ຍ䛘
䛶䚸ඹྠ◊✲ᣐⅬᒎ㛤ඹྠ◊✲ B 䜢 3 ௳䠄㜰኱⏘◊ ୰㇂࿴ᙪඛ⏕䞉㛗ᓮ኱⸆ ᒣྜྷ㯞Ꮚඛ⏕䚸໭኱㟁Ꮚ◊ ୕
⃝ᘯ᫂ඛ⏕䡡༓ⴥ኱ᕤ ၈ὠᏕඛ⏕䚸ᮾᕤ኱໬⏕◊ ⚟ᓥᏕ඾ඛ⏕䞉៞᠕኱⩚᭯㒊༟ඛ⏕䠅䚸ྡ኱ᶔ⏣ඛ⏕䚸㜰
኱᳃ඛ⏕䚸㛗ᓮ኱ᒣᮏඛ⏕䚸ᮾ኱㧗஭ඛ⏕䚸ྡ኱ὸ἟ඛ⏕䚸ᮾி⌮኱㫽㉺ඛ⏕䛸䛾ᇶ┙ඹྠ◊✲䜢᥎㐍䛧䛯䚹
㻞䠊㻌 ⏕య㧗ศᏊ䛾ືⓗᣲື䛾ゎᯒ䜢┠ᣦ䛧䛯㧗ឤᗘ䞉㧗᫬㛫᫬㛫ศゎ෇஧Ⰽ ᐃἲ䠄㻯㻰䠅䛾㛤Ⓨ䛸ᛂ⏝㻌
䛣䜜䜎䛷ᡃ䚻䛿ᴃ෇೫ග䜢⏝䛔䜛෇஧Ⰽ䠄CD䠅 ᐃἲ䜢ᇶ䛻᫬㛫ศゎ෇஧Ⰽ ᐃἲ䛾㛤Ⓨ䜢⾜䛔䚸⏕య
㧗ศᏊ䛾ືⓗᣲື䛾ゎᯒ䜔䚸ගບ㉳≧ែ䛾䜻䝷䝸䝔䜱᳨ฟ䜢┠ᣦ䛧䛯㐣Ώ CD 䝇䝨䜽䝖䝹䛾᳨ウ䜢⾜䛳䛶䛝
䛯䚹୍᪉䚸ගບ㉳≧ែ䛾䜻䝷䝸䝔䜱᳨ฟ䛾ほⅬ䛛䜙䛿䚸ගບ㉳≧ែ䛻䛚䛡䜛䜻䝷䝹ศᏊ䛛䜙䛾෇೫ගⓎග
䠄CPL䠅ศගἲ䜢⏝䛔䜛஦䜒㔜せ䛺ㄢ㢟䛷䛒䜛䛯䜑䚸ᮏᖺᗘ䛿 CPL 䛻╔┠䛧䛯◊✲䝔䞊䝬䜢᪂䛯䛻❧䛱ୖ䛢
䛯䚹
㏆ᖺ䚸CPL 䜢ຠ⋡䜘䛟Ⓨ䛩䜛ᑠศᏊ䛾㛤Ⓨ䛜 3D 䝕䜱䝇
䝥䝺䜲⏝ග※䜈䛾ᛂ⏝䛾ほⅬ䛛䜙㔜せど䛥䜜䛴䛴䛒䜛䚹
ᮏᖺᗘ䛻䛚䛔䛶䚸ᡃ䚻䛿䝘䝣䝍䝺䞁䝆䜲䝭䝗 2 㔞య
((M)-D2, (P)-D2) 䛾ගບ㉳୍㔜㡯≧ែ䛛䜙䚸㧗ຠ⋡䛾෇
೫ගⓎග䛜Ⓨ䛫䜙䜜䜛䛣䛸䜢ᐇ㦂ⓗ䛻☜ㄆ䛧䚸䛥䜙䛻䛭䛾
䝇䝨䜽䝖䝹ゎ㔘䜢⾜䛳䛯䚹D2 䛾㟁Ꮚບ㉳≧ែ䛿䜶䜻䝅䝬
䇷䛻┦ᙜ䛩䜛䛸⪃䛘䜙䜜䚸䛭䛣䛛䜙㧗ຠ⋡䛺 CPL 䜢Ⓨ䛩䜛
䛸ᐃᛶⓗ䛻䛿ゎ㔘䛥䜜䛯䚹D2 䛿䝅䞁䝥䝹䛺ศᏊᵓ㐀䛷䛿
䛒䜛䛜䚸෇೫ගⓎග䛾␗᪉ᛶ 䠄glum䠅 䛿䛣䜜䜎䛷ከᩘሗ
࿌䛥䜜䛶䛝䛯ᑠศᏊ䛛䜙䛾 glum 䛸ẚ㍑䛧䛶䜒༑ศ䛻኱䛝䛟䚸
௒ᚋ㧗⢭ᗘ䛾㔞Ꮚ໬Ꮫィ⟬䜔᫬㛫ศゎ䛾 CPL  ᐃ䛺䛹
䜢㏻䛧䛯Ⓨග䝯䜹䝙䝈䝮䛾ᐃ㔞ⓗ䛺ゎ㔘䜢⾜䛖䛣䛸䛷䚸㧗ຠ
⋡䛛䛴 glum 䛜䜘䜚ྥୖ䛧䛯ศᏊタィ䛾ᣦ㔪䛜ᚓ䜙䜜䜛䜒䛾

Fig. 2. ...