⑌ᝈ䝰䝕䝹䝬䜴䝇䛾⾑Ύ䛸P450㓝⣲䛸䛾┦஫స⏝䜢฼⏝䛧䛯⅖⑕ᛶ⑌ᝈデ᩿ἲ䛾㛤Ⓨ◊✲ᮇ㛫䠖2018-2019ᖺ‫ڂݜ‬ഐ‫ܢ‬ʀ໪దԎ঳ൕԢͶΓΖP450͹௒ઇʤྭʥ
Zordoky et al. Curr.Drug Metab.2009 ;10(2):164-78෨րฦԎ঳੓ௐ࣮‫׳‬ɼ‫ؖ‬ઇϨΤϜοɼ͗Ξɼ౸೚බɼਝ࣮‫׳‬ɼ݄͑ͮ੓
ৼ෈સ etc..

Ԏ঳੓γ΢φΩ΢ϱ࢐ԿηφϪη

Nf-Ж%͹‫׈‬੓Կ
P450͹൅‫ྖݳ‬ʀ‫׈‬੓͹௒ઇҲ‫ࡑݳ‬ɼ౸೚බ͹ਏஇͶͺɼଡ਼͹‫ߴࠬݗ‬໪ΝࣰࢬͤΖචགྷ͍͗Ζ͞ͳ͖Δɼ࣎ؔͳαηφΝགྷͤΖɽΉͪɼҲ෨Ͷͺ‫ं׳‬΃͹ෝ୴͗୉͘͏‫ࠬݗ‬घ๑΍ߨΚΗͱ͏
Ζ͞ͳ͖ΔɼΓΕ؈ส͵ਏஇघ๑͗๮ΉΗͱ͏Ζɽ઎͹‫͖ڂݜ‬ΔɼԎ঳੓࣮‫࣎׳‬Ͷͺ࣮‫׳‬ಝҡదͶP450͹൅‫ྖݳ‬Ώ߮ો‫׈‬੓஍͗ร
ԿͤΖࣆ͗எΔΗͱ͏Ζ( Chaluvadi MRet al, 2008 )ɽ
ͨ͞Ͳຌ‫Ͳڂݜ‬ͺɼϐφP450߮ોͳ‫ܮ‬ޭ੓P450‫ͳ࣯خ‬͹ൕԢ‫ܧ‬Ͷଲ͢ͱɼᶙ‫ܗ‬౸೚බϠυϩϜΤη݄ੜΝ‫ͦ͠߻ڟ‬Ζ͞ͳͲɼ࣮‫׳‬ಝҡద͵ώ΢ΨϜʖΩʖ͹֋൅Νߨͮͪɽࣰ‫֕ݩ‬གྷ

1.

P450ͶΓͮͱେः͠ΗΖɼ݄ੜ੔෾஦͹P450ൕԢ෼࣯ͳ‫߻ڟ࣯͗خޭܮ‬2.

‫ౕکޭܮ‬͹଎ఈͶΓΕɼ݄ੜ੔෾஦͹P450ൕԢ෼࣯Ν‫ݗ‬ड़݃Վͳߡࡱ݊৙ϜΤηͳ࣮‫׳‬ϜΤηͲͺɼᶙ‫ܗ‬౸೚බ൅঳࣎ͶCYP1A1Ͷ
͕͏ͱҡ͵ΖP450‫ޭܮ‬Ϗνʖϱ͗‫ݡ‬ΔΗͪɽΓͮͱɼຌघ๑͗I‫ܗ‬౸೚බ͹ώ΢ΨϜʖΩʖͳ͵ΖՆ೵੓͗ࣖࠨ͠Ηͪɽ⚄ᡞ኱Ꮫ኱Ꮫ㝔 ㎰Ꮫ◊✲⛉ ⎔ቃ≀㉁⛉Ꮫ◊✲ᐊ௒▼ ᾈṇ 㐃⤡ඛ㸸himaish@kobe-u.ac.jpேᕤ⏕య⭷䜢฼⏝䛧䛯㧗ឤᗘ⏕యศᏊィᢏ⾡◊✲ᮇ㛫䠖㻞㻜㻜㻥䡚㻞㻜㻝㻤ᖺ◊✲⫼ᬒ䞉┠ⓗ⎔ቃ୰䜔⾑ᾮ䛾䜘䛖䛻㧗⃰ᗘ䛻ዃ㞧ศᏊ䛜Ꮡᅾ䛩䜛᮲௳䛷≉ᐃ䛾⏕యศᏊ䜢㧗ឤᗘィ 䛩䜛䛣䛸䛿䚸ᅔ㞴䛷䛒䜛䚹ᡃ䚻䛿䚸⏕య⭷䜢ᶍೌ䛧䛯ேᕤ⏕య⭷䛸䝘䝜✵㛫䜢⤌䜏ྜ䜟䛫䜛䛣䛸䛷䚸㧗⃰ᗘ䛻ዃ㞧ศᏊ䛜Ꮡᅾ䛩䜛᮲௳䛷䜒⏕యศᏊ䜢㧗ឤᗘ䛷ィ 䛷䛝䜛ᢏ⾡䜢㛤Ⓨ䛧䛯䚹ᑗ᮶ⓗ䛻䛿䚸⏕⌮ⓗ᮲௳䛷䜒䚸ಶ䚻䛾ศᏊ䜢ィ 䛧䠄䠍ศᏊィ 䠅䚸デ᩿䛻฼⏝䛩䜛䛣䛸䛜ྍ⬟䛻䛺䜛䜒䛾䛸ᮇᚅ䛥䜜䜛䚹㉸㧗ឤᗘ᳨ฟ⏕య⭷䛾≉ᚩ
¾ ὶືᛶ䠄ศᏊ䛾2ḟඖᣑᩓ䠅¾ 㠀≉␗ⓗ྾╔䛾ᢚไ⏕య⭷䛾᝟ሗఏ㐩ᶵᵓ䝅䜾䝘䝹ศᏊ」ྜయ

ቑᖜཷᐜయ⏕య⭷䛸䝘䝜✵㛫䜢⤌䜏ྜ䜟䛫䛯᪂䛧䛔⏕యศᏊィ ᢏ⾡䜹䜲䝁䠖Bombyx moriᐇ㦂ᴫせཌ䛥ᩘ༑䝘䝜䝯䞊䝖䝹䛾᥋╔ᒙ䜢⏝䛔䛯䚸⭷䛸㻼㻰㻹㻿䛾᥋ྜ䝟䝍䞊䞁໬ேᕤ⏕య⭷䝘䝜䜼䝱䝑䝥ᵓ㐀䜢⏝䛔䛯⏕యศᏊィᶆⓗศᏊ㑅ᢥⓗศᏊ㍺㏦

䝫䝸䝬䞊⬡㉁⭷ ⏕య⬡㉁⭷ศᏊㄆ㆑䛻䜘䜛㑅ᢥⓗ⤖ྜ⤖ᯝ䛸⪃ᐹMicrochannelaᶆⓗศᏊ䛾㑅ᢥⓗ᳨ฟ

Nanogap୺せ䛺⤖ᯝ䛸ᒎᮃ䠖

Nanogapz㧗⃰ᗘ䛺ዃ㞧ศᏊ䠄∵⾑Ύ䜰䝹䝤䝭䞁䠅䛜Ꮡᅾ䛩䜛⁐ᾮ୰䛷䚸ᶆⓗศᏊ䠄䝁䝺䝷ẘ⣲䠅䜢㑅ᢥⓗ䛛䛴㧗ឤᗘ䛻᳨ฟ䛥䜜䛯䚹bᶆⓗศᏊ䠄䝁䝺䝷ẘ⣲䠅

120

1000

a (microchannel)b (nanogap)

800
600
400
200

Fluorescence intensityዃ㞧ศᏊ䠄∵⾑Ύ䜰䝹䝤䝭䞁䠅Fluorescence intensity

1200b (enlarged)

1008060402000020406080 100 120 140 160

Position (Pm)0㧗ឤᗘ᳨ฟ䠄⺯ග䠅

20406080 100 120 140 160z䛂䝟䝍䞊䞁໬ேᕤ⏕య⭷䛃䛸䛂䝘䝜䜼䝱䝑䝥ᵓ㐀䛃䛿䚸⏕య⭷䛾≉ᛶ䛸䝘䝜✵㛫䜢⼥ྜ䛩䜛䛣䛸䛷䚸⏕యศᏊ䛾㉸㧗ឤᗘィ 䜢ྍ⬟䛻䛧䚸⎔ቃ୰≀㉁䜔యෆ䛾⑌ᝈ䝬䞊䜹䞊䛾᳨ฟ䜢ᐇ⌧䛩䜛䚹

Position (Pm)⚄ᡞ኱Ꮫ኱Ꮫ㝔㻌 ㎰Ꮫ◊✲⛉㻌 ⎔ቃ≀㉁⛉Ꮫ◊✲ᐊ᳃ᇉ㻌 ᠇୍㻌 㐃⤡ඛ䠖ŵŽƌŝŐĂŬŝΛƉŽƌƚ͘ŬŽďĞͲƵ͘ĂĐ͘ũƉⓎ⾲ㄽᩥ
1. Tanabe, M., Ando, K., Komatsu, R., Morigaki, K. "Nanofluidic biosensor created by bonding
patterned model cell membrane and silicone elastomer with silica nanoparticles", Small 14 (49),1802804, (2018)
2. Nishimura, T., Tamura, F., Kobayashi, S., Tanimoto, Y., Hayashi, F., Sudo, Y., Iwasaki, Y., Morigaki, K.
"Hybrid model membrane combining micropatterned lipid bilayer and hydrophilic polymer
brush", Langmuir 33 (23), 5752-5759, (2017)
3. Ando, K., Tanabe, M., Morigaki, K. "Nanometric gap structure with fluid lipid bilayer for theselective transport and detection of biological molecules", Langmuir 32 (31), 7958-7964, (2016)
4. Tanimoto, Y., Okada, K., Hayashi, F., Morigaki, K. "Evaluating the raftophilicity of rhodopsin
photoreceptor in a patterned model membrane", Biophys. J. 109 (11), 2307-2316, (2015)
5. Yamada, M., Imaishi, H., Morigaki, K. "Microarrays of phospholipid bilayers generated by inkjetprinting", Langmuir 29 (21), 6404-6408, (2013)
6. Morigaki, K., Mizutani, K., Saito, M., Okazaki, T., Nakajima, Y., Tatsu, Y., Imaishi, H. "Surfacefunctionalization of a polymeric lipid bilayer for coupling a model biological membrane withmolecules, cells, and microstructures", Langmuir 29 (8), 2722-2730, (2013)
7. Morigaki, K., Mizutani, K., Kanemura, E., Tatsu, Y., Yumoto, N., Imaishi, H. "Photo-regulation ofcytochrome P450 activity by using caged compound", Anal. Chem. 84 (1), 155-160, (2012)
8. Okazaki, T., Inaba, T., Tatsu, Y., Tero, R., Urisu, T., Morigaki, K. "Polymerized lipid bilayers on solid
substrate: Morphologies and obstruction of lateral diffusion", Langmuir 25 (1), 345-351, (2009)

Ꮫ఍Ⓨ⾲
1. Morigaki, K. “Reconstituting Membrane Proteins in a Patterned Model Membrane”, Workshop onProteins in Artificial Membranes, 2018ᖺ5᭶30᪥, Tulln, Austria
2. Morigaki, K., Tanabe, M., Komatsu, R., Ando, K. “Nanometric gap structure for selective biosensing
created with patterned lipid bilayer, silicone elastomer, and silica nanoparticles”, 255th American
Chemical Society National Meeting, 2018ᖺ3᭶18-22᪥, New Orleans, USA≉チ≉チ6400483ྕ䚸Ⓨ᫂⪅䠖᳃ᇉ ᠇୍䛂䝘䝜䜼䝱䝑䝥ᵓ㐀ᆺᇶᯈ䛃䚸Ⓩ㘓᪥䠖2018ᖺ9᭶14᪥
≉チ5713318ྕ䚸Ⓨ᫂⪅䠖᳃ᇉ ᠇୍䚸㐩ྜྷ㑻䚸ᖖ㗰䚸௒▼ᾈṇ䛂ከᵝ䛺䝏䝖䜽䝻䝮P450ศᏊ✀䛾㓝⣲άᛶ䜢⥙⨶ⓗ䛛䛴㧗ຠ⋡䛷 ᐃ䛩䜛᪉ἲཬ䜃䜻䝑䝖䛃䚸Ⓩ㘓᪥䠖2015ᖺ3᭶20᪥
≉チ5532229ྕ䚸Ⓨ᫂⪅䠖᳃ᇉ ᠇୍䚸ᒸᓮᩗ䚸㐩ྜྷ㑻䚸୰ᓥⰾᾈ䛂䝫䝸䝬䞊⬡㉁஧ศᏊ⭷䜢⏝䛔䛯ᶵ⬟ᛶᇶᯈ䛃䚸Ⓩ㘓᪥䠖2014ᖺ5᭶9᪥≉チ4150793ྕ䚸Ⓨ᫂⪅䠖᳃ᇉ᠇୍䚸䛂ග㔜ྜᛶ⬡㉁⭷䛻䜘䜛⭷ෆศᏊ䛾Ỉᖹᣑᩓไᚚ䛃䚸Ⓩ㘓᪥䠖ᖹᡂ20
ᖺ7᭶11᪥䚸ฟ㢪᪥䠖ᖹᡂ16ᖺ3᭶12᪥ඹྠ◊✲ඛி㒔኱Ꮫ䜴䜲䝹䝇䞉෌⏕་⛉Ꮫ◊✲ᡤ䠈 ᒱ㜧኱Ꮫ◊✲᥎㐍䞉♫఍㐃ᦠᶵᵓ ⏕࿨䛾㙐⤫ྜ◊✲䝉䞁䝍䞊኱㜰኱Ꮫ኱Ꮫ㝔ᇶ♏ᕤᏛ◊✲⛉䠈 ᗈᓥ኱Ꮫ኱Ꮫ㝔⌮Ꮫ⣔◊✲⛉䠈 රᗜ┴❧኱Ꮫ኱Ꮫ㝔ᕤᏛ◊✲⛉䝃䞁䝖䝸䞊⏕࿨⛉Ꮫ㈈ᅋ ⏕≀᭷ᶵ⛉Ꮫ◊✲ᡤ䠈 University of Siegen