JP4433658B2 - Electronic equipment - Google Patents

Description

【００３９】
このタンパク質の立体構造はBulloughらによってＸ線構造解析を用いて決定されており（(56)P.A.Bullough,F.M.Hughson,J.J.Skehel,and D.C.Wiley:"Structure of influenza haemagglutinin at the Ph of membrane fusion",Nature(London),371,37-43,(1994)) 、その情報はProtein Data Bank(PDB,http://www.rcsb.org/pdb/）に登録されている（登録ＩＤ：１ＨＴＭ）。このタンパク質は３本の長い（１０ｎｍ程度）α−ヘリックスを含んでいる。ここでは４１番目の残基Ｔｈｒから１０４番目の残基Ａｓｎまでの６４残基で構成されている１本のα−ヘリックスを取り上げ、その一部のアミノ酸をＬｎｋに変更することを考える。
【００４０】
α−ヘリックスは１巻きを３．６残基で構成しており、そのピッチは０．５４ｎｍである。そこで、７残基ごとにアミノ酸をＬｎｋに変更し、その側鎖に直径１ｎｍ程度のＣｄＳｅ／ＺｎＳ量子ドットを結合すると、図４に示すように、そのＣｄＳｅ／ＺｎＳ量子ドットは互いに近接して鎖状に並んだ構造を取ることがわかる。この場合、９箇所の残基を変更することができて、具体的には（４２：Ｇｌｎ）、（４９：Ａｓｎ）、（５６：Ｉｌｅ）、（６３：Ｐｈｅ）、（７０：Ｐｈｅ）、（７７：Ｉｌｅ）、（８４：Ｖａｌ）、（９１：Ｌｅｕ）、（９８：Ｌｅｕ）の各アミノ酸残基を全てＬｎｋに変更する。α−ヘリックスは比較的安定な構造であり、少数の残基の変更では構造を保つことが期待できる。
【００４１】
この設計に基づいて、上記の転写−翻訳による生合成および側鎖と量子ドットとの結合手法を用いることで、１次元鎖の構造を持つ結合量子ドットを構築することができる。
【００４２】
（４）らせん構造
次に、らせん構造を持つ結合量子ドットを構築する。元となるタンパク質としてラクトース結合破傷風毒素のＨｃフラグメントを取る。そのＰＤＢのＩＤは１ＤＬＬである。このタンパク質の立体構造はEmsleyらによって決定された（(57)P.Emsley,C.Fotinou,I.Black,N.F.Fairweather,I.G.Charles,C.Watts,E.Wewitt,and N.W.Isaacs:"The structures of the H(C)fragment of tetanus toxin with carbohydrate subunit complexes provide insight into canglioside binding",J.Biol.Chem.275,8889,(2000))。このタンパク質は典型的な２次構造モチーフの一つである、ゼリーロール・バレルを取る。その様子を図５の破線囲み部に示す。これは、安定な２次構造のβ−ストランドが１７本集まってバレルを形成している構造で、少数のアミノ酸の入れ替えに対して比較的安定と考えられる。この２次構造モチーフは、８８５番目の残基から１０９２番目の残基までで構成されている。注目するβ−ストランドは１５本で、アミノ酸配列のＮ末端からＣ末端の方向で現れる順に２次構造に付けた番号でそれぞれ、４（８８５−８８８），５（８８９−８９２），７（８９５−８９８），９（９０５−９０８），１５（９３３−９３６），２１（９５０−９５７），２５（９７３−９７８），２７（９９０−９９６），２９（９９９−１００５），３１（１０１１−１０１７），３３（１０３２−１０３８），３５（１０４３−１０４８），３７（１０５１−１０５７），３９（１０６９−１０７５），４１（１０８４−１０９２）（括弧内はストランドを構成する残基の番号）である。
【００４３】
図５に示すように、らせん状に量子ドットを配置するために、４のβ−ストランドから始めて、４→４１→２１→３３→３５→３７→３１→２９→２７→２５→３９→１５→９→７→５→４１→２１→３３→３５→３７→３１→２９→２７→２５→３９（下線はらせんの２巻き目で通るストランドを表す）のようならせん構造を構築することを考える。そのため各ストランドで、４（８８６：Ｉｌｅ），４１（１０８５：Ｓｅｒ，１０９１：Ｉｌｅ），２１（９５１：Ｔｈｒ，９５５：Ｔｒｐ），３３（１０３３：Ｐｈｅ，１０３７：Ｔｈｒ），３５（１０４４：Ａｌａ，１０４８：Ｉｌｅ），３７（１０５２：Ｌｅｕ，１０５６：Ａｌａ），３１（１０１２：Ａｒｇ，１０１６：Ｐｈｅ），２９（１０００：Ｌｅｕ，１００４：Ｌｅｕ），２７（９９１：Ｔｒｐ，９９５：Ｌｅｕ），２５（９７４：Ｔｙｒ，９７８：Ｓｅｒ），３９（１０７０：Ｉｌｅ，１０７４：Ｌｅｕ），１５（９３４：Ｉｌｅ），９（９０６：Ｖａｌ），７（８９６：Ｉｌｅ），５（８９０：Ａｓｐ）、の各残基をそれぞれＬｎｋへと変更したアミノ酸配列を設計する。
【００４４】
この設計から上記と同様に、生合成および量子ドットの結合を行うことでらせん構造を持った結合量子ドット系を作製することができる。この手法を用いて量子細線の周りにらせん構造を持った結合量子ドットを配置することで、新規な機能を持ったデバイス（(58)R.Ugajin:"Charge transfer device",US Patent 5,828,090(October27,1998))を実現することもできる。
【００４５】
（５）分岐構造
次に、分岐構造を構築する。元のタンパク質としては、ペニシリンに作用するＤＤ−ペプチダーゼ酵素を取る。この立体構造は、Kelly ら((59)J.A.Kelly,J.R.Knox,H.Zhao,J.M.Frere,and J.M.Ghuysen:"The refined crystallographic structure of a DD-peptidase penicillin-target enzyme at 1.6Å resolution",J.Mol.Biol.,254,223,(1995))によって決定されている（ＰＤＢ ＩＤ：３ＰＴＥ）。上記と同様な手順で２次構造に付けた番号で、５４（３１７−３２３）、４（２５−３２）、６（３５−４２）（括弧内はストランドを構成する残基の番号）のβ−ストランドを考えて、５４−４で１分岐、４−６で２分岐となる構造を設計する（図６）。
【００４６】
具体的には各ストランドで、５４（３２０：Ｔｈｒ）、４（２６：Ａｌａ，３０：Ｖａｌ）、６（３５：Ｔｈｒ，３７：Ｈｉｓ，３９：Ｌｅｕ，４１：Ｇｌｕ）、の各残基をそれぞれＬｎｋに変更したアミノ酸配列を設計する。
これより、上記と同様の手続きで分岐構造を持った結合量子ドットを作製することができる。
【００４７】
（６）高次構造
代表的な高次構造である多重化階層構造やフラクタル構造は、前節までの３つの基本構造、らせん構造、分岐構造、１次元鎖状構造を組み合わせることで構成することができ、具体例を挙げると、多重巻きらせん構造は、らせん構造を基として遠方との結合として結合させる両要素に分岐を入れてその間を１次元鎖で結合すればよいことがわかる。また、フラクタル構造も分岐と１次元鎖とを自己相似的に組み合わせることで実現することができる。よってこれらの高次構造もここでの手法により作製可能であることがわかる。
【００４８】
第２の実施形態
この第２の実施形態においては、微小構造体と結合したポリヌクレオチド鎖を含む複数のポリヌクレオチド鎖を含み、その複数のポリヌクレオチド鎖における、少なくとも微小構造体と結合したポリヌクレオチド鎖を含む少なくとも一対のポリヌクレオチド鎖が相補的な塩基対で結合することにより取る立体構造により１つまたは複数の微小構造体の空間における配置が決められている機能材料について説明する。
【００４９】
（１）ＤＮＡ鎖と量子ドットとの結合
ここでは、図７に示すように、ＤＮＡ鎖４に対して、ＣｄＳｅ／ＺｎＳ量子ドットを結合させることを考える。このＣｄＳｅ／ＺｎＳ量子ドットの詳細は第１の実施形態で述べたとおりである。この場合、リンカーとして−Ｓ−（ＣＨ₂ ）₆ −を用いることで、ＣｄＳｅ／ＺｎＳ量子ドットをＤＮＡ鎖の末端に結合させることができる（上記文献(31)) 。
【００５０】
ＤＮＡ鎖４の任意の位置にＣｄＳｅ／ＺｎＳ量子ドットを結合させるためには、ＤＮＡ鎖４が相補的な塩基配列を持ったＤＮＡ鎖と対を作ることを利用する。１本の長いＤＮＡ鎖を準備して、その目的の位置に相補的な塩基配列を持つ短いＤＮＡ鎖を持ってくる。そして、図８に示すように、その短いＤＮＡ鎖の末端に上記のリンカーを用いてＣｄＳｅ／ＺｎＳ量子ドットを結合し、それを長いＤＮＡ鎖に結合させるという手順を取ればよい。短いＤＮＡ鎖の長さと本数とを変化させることにより、任意の個数のＣｄＳｅ／ＺｎＳ量子ドットを長いＤＮＡ鎖の塩基配列の任意の位置に置くことができることもわかる。
【００５１】
（２）１次元鎖状結合構造
まず、構造を構築する上で基本的な１次元鎖状結合構造を持った量子ドットを具体的に作製する。既に述べたように、この系は単純であるが理論的に興味深い結果も得られている（上記文献(54)(55)) 。
【００５２】
通常の２本の相補的なＤＮＡ鎖よりなる２重らせんを考える。ＤＮＡ分子は細胞内では主としてＢ型と呼ばれる構造を取ることが知られている（(60)T.A.Brown:"Genomes" (BIOS Scientific Publishers,Oxford,1999)）。この構造では、らせんの直径は２．３７ｎｍで、１０塩基対で１ピッチ（３．４ｎｍ）となる。また、ここで用いるＣｄＳｅ／ＺｎＳ量子ドットの典型的なサイズは１ｎｍから十数ｎｍである。そこで、長いＤＮＡ鎖として１００塩基の長さのものを取り、短いＤＮＡ鎖として１０塩基の長さで、その５´−末端にＣｄＳｅ／ＺｎＳ量子ドットを結合したものを１０本取ることとする。図９に示すように、ここでは、短いＤＮＡ鎖はそれぞれ適切な塩基配列を取り、長いＤＮＡ鎖と相補的に塩基対との結合で並べることができるものとする。
【００５３】
こうしてできた２重鎖は１０周期のらせん構造を取り、その時上記のように結合したＣｄＳｅ／ＺｎＳ量子ドットは図１０に示すように１次元鎖状構造となることがわかる。この時、ＣｄＳｅ／ＺｎＳ量子ドット間の中心間の距離は約３．４ｎｍとなるので、典型的なＣｄＳｅ／ＺｎＳ量子ドットのサイズの範囲内で結合させることが可能であることもわかる。
【００５４】
（３）らせん構造
次に、ＣｄＳｅ／ＺｎＳ量子ドットをらせん構造に配置することを考える。そこで、上記（２）と同じ状況の下、長いＤＮＡ鎖として１１０塩基の長さのものを取り、短いＤＮＡ鎖として１１塩基の長さで、その５´−末端にＣｄＳｅ／ＺｎＳ量子ドットを結合させたものを１０本取ることとする。
【００５５】
こうしてできた２重鎖が１１周期のらせん構造を取るとき、上記のように結合したＣｄＳｅ／ＺｎＳ量子ドットは図１１に示すように１周期のらせん構造となることがわかる。この時、ＣｄＳｅ／ＺｎＳ量子ドット間の中心間の距離は約４．０３ｎｍとなるので、この場合も典型的なＣｄＳｅ／ＺｎＳ量子ドットのサイズの範囲内で結合させることが可能である。
【００５６】
また、１塩基長のＤＮＡ鎖ごとにＣｄＳｅ／ＺｎＳ量子ドットを結合させることにすれば、量子ドットの中心間の距離が約１．５３ｎｍのらせん構造となることもわかる。
【００５７】
更に、異なるＤＮＡ分子の立体構造であるＡ型（らせんの直径２．５５ｎｍ、ピッチは１１塩基対で３．２ｎｍ）に対しても同様にらせん構造を設計することができる。
【００５８】
（４）分岐構造
次に、分岐構造を構築する。ここでは、２分岐を持ったＤＮＡ分子の足の先端にＣｄＳｅ／ＺｎＳ量子ドットを結合させたものを部品として、それをつなぎ合わせて分岐構造を構成することとする。
【００５９】
まず、図１２に示すように、２分岐を持ったＤＮＡ分子を設計する。通常の２重らせんを構成するために必要となる２本のＤＮＡ鎖に加えて、更にもう１本ＤＮＡ鎖を準備する。それらのＤＮＡ鎖をＡ，Ｂ，Ｃと名づける。また、それぞれのＤＮＡ鎖を二つの部分に分け、それぞれをＡ（Ｂ，Ｃ）₁ ，Ａ（Ｂ，Ｃ）₂ と表すこととする。この３本のＤＮＡ鎖が部分相補鎖同士結合し、うまく１つの構造を作るためには、次の条件を満たせばよいことがわかる。
【００６０】
Ａ₁ ＝Ｂ₂ バー
Ｂ₁ ＝Ｃ₂ バー （２）
Ｃ₁ ＝Ａ₂ バー
ここで、Ｘバーは部分鎖Ｘの相補鎖であることを表している。具体的には、分岐部分からそれぞれ１０塩基対の長さの２重らせんが出ているものとする。その先端にＣｄＳｅ／ＺｎＳ量子ドットを結合させたとすると、量子ドットの中心間の距離は約５．８８ｎｍとなり、設計可能なサイズである。また、実際上はＤＮＡ鎖同士を選択的に結合させるために、ある部分鎖は目的の部分鎖以外とは相補鎖の関係にならないように設計する。
【００６１】
上記の手法で２分岐ＤＮＡを作る際に１０塩基に一つＣｄＳｅ／ＺｎＳ量子ドットを結合させることにすれば、ＣｄＳｅ／ＺｎＳ量子ドットの２分岐構造を作ることができる。
【００６２】
更に、このＣｄＳｅ／ＺｎＳ量子ドットの結合した２分岐ＤＮＡを７つ準備して、Zhang and Seeman((61)J.Am.Chem.Soc.,114,2656-2663,(1992)) に述べられている手法によってそれらを図１３のように結合することで、３段の２分岐構造を作製することができる。
【００６３】
この手法では、平面的な分岐構造だけが構成可能であるが、実際には２分岐以外の３分岐、４分岐の構造も構成可能であるため、それらを結合し、かつ前節で述べたらせん構造を適宜途中に導入することにより、３次元空間中の分岐構造も構成可能であることがわかる。これによりフラクタル構造も作製することができる。
【００６４】
（５）多重巻きらせん構造
従来技術の項で述べたように、多重巻きらせん構造は、基本となる１次元鎖とらせん構造とに加えて、長周期の要素間結合を取ることで構成されている。そこで、上記（３）で構成したらせん構造を基本として、上記（４）の２分岐構造を長周期で導入して、その分岐間を１次元鎖状構造で結合すれば、２重巻きらせん構造を構成することができる。同様に、更に高次の長周期構造を導入することは可能で、一般の多重巻きらせん構造も構成することができる。
【００６５】
（６）応用
ここでの技術を用いることで、半導体量子ドットを、空間的に構造を持った状態に配置した結合量子ドットを作製することができる。例えば、量子細線の周りにらせん構造を持った結合量子ドットを配置することで、新規な機能を持ったデバイスを実現することができることが知られている（上記文献(39)）。
【００６６】
また、結合量子ドットは量子計算((62)P.Benioff:"The Computer as a Physical System:A Microscopic Quantum Mechanical Hamiltonian Model of Computers as Represented by Turing Machines",J.Stat.Phys.,22,563-591,(1980) (63)R.Feynman:"Quantum Mechanical Computers",Opt.News,11,11-20,(1985) (64)D.Deutsch:"Quantum Theory,the Church-Turing Principle,and the Universal Quantum Computer",Proc.Roy.Soc.London,Ser.A400,97-117,(1985) (65)M.A.Nielsen and I.L.Chuang:"Quantum Computation and Quantum Information",(Cambridge University Press,Cambridge,UK,2000)) の実現が期待される系としても良く研究されている((66)A.Barenco,D.Deutsch,and A.Ekert:Phys.Rev.Lett.,74,4083,(1995) (67)D.Loss and D.P.DiVincenzo:"Quantum Computation with Quantum Dots",Phys.Rev.A57,120,(1998) (68)V.N.Golvach and D.Loss:"Electron Spins in Artificial Atoms and Molecules for Quantum Computing",Special Issue of Semiconductor Science and Technology,"Semiconductor Spintronics",ed.H.Ohno,(2002))。ここで述べた技術を用いることにより、１次元的な結合だけでなく高次の結合構造を持った結合量子ドットを構成することができるため、従来知られている量子アルゴリズム((69)D.Deutsch and R.Jozsa:"Rapid Solution of Problems by Quantum Computation",Proc.Roy.Soc.London,A439,553-558,(1992) (70)P.W.Shor:" Algorithms for Quantum Computation:Discrete Logarithms and Factoring",Proceedings of the 35th Annual Symposium on Foundation of Computer Science,124-134,(1994) (71)L.K.Grover:"A fast quantum mechanical algorithm for database search",Proceedings of the 28th Annual ACM Symposium on the Theory of Computing,212-219,(1996))だけでなく、結合の幾何学的な性質を活かした全く新しい量子アルゴリズムの実現が期待できる。
【００６７】
以上、この発明の実施形態につき具体的に説明したが、この発明は、上述の実施形態に限定されるものではなく、この発明の技術的思想に基づく各種の変形が可能である。
【００６８】
例えば、上述の実施形態において挙げた数値、材料、構造、形状などはあくまでも例にすぎず、必要に応じてこれらと異なる数値、材料、構造、形状などを用いてもよい。
【００６９】
【発明の効果】
以上説明したように、この発明によれば、微小構造体が選択的に結合する側鎖を有するアミノ酸を所定位置に組み入れたアミノ酸配列からなるペプチド結合鎖の取る立体構造により１つまたは複数の微小構造体の空間における配置を決め、あるいは、微小構造体と結合したポリヌクレオチド鎖を含む複数のポリヌクレオチド鎖を含み、これらの複数のポリヌクレオチド鎖における、少なくとも微小構造体と結合したポリヌクレオチド鎖を含む一対のポリヌクレオチド鎖が相補的な塩基対で結合することにより取る立体構造により１つまたは複数の微小構造体の空間における配置を決めるので、豊富な物性を発現する機能材料を安価に大量に得ることができ、この機能材料を用いて高機能の各種の電子装置あるいは量子装置を実現することができる。
【図面の簡単な説明】
【図１】この発明の第１の実施形態において用いるＣｄＳｅ／ＺｎＳ量子ドットの構成を示す略線図である。
【図２】この発明の第１の実施形態において用いるＣｄＳｅ／ＺｎＳ量子ドットのエネルギーバンドを示す略線図である。
【図３】この発明の第１の実施形態において二つのＣｄＳｅ／ＺｎＳ量子ドットが近接したときのトンネル効果を説明するための略線図である。
【図４】この発明の第１の実施形態においてα−ヘリックスの７アミノ酸残基ごとにＣｄＳｅ／ＺｎＳ量子ドットが結合したものを示す略線図である。
【図５】この発明の第１の実施形態においてゼリーロール・バレルにらせん状にＣｄＳｅ／ＺｎＳ量子ドットが結合したものを示す略線図である。
【図６】この発明の第１の実施形態においてゼリーロール・バレルにらせん状にＣｄＳｅ／ＺｎＳ量子ドットが結合したものを示す略線図である。
【図７】この発明の第２の実施形態においてＣｄＳｅ／ＺｎＳ量子ドットにＤＮＡ鎖が結合した様子を示す略線図である。
【図８】この発明の第２の実施形態においてＤＮＡ鎖にリンカーを用いてＣｄＳｅ／ＺｎＳ量子ドットが結合されたものを示す略線図である。
【図９】この発明の第２の実施形態においてＤＮＡ鎖にリンカーを用いてＣｄＳｅ／ＺｎＳ量子ドットが結合されたものを示す略線図である。
【図１０】この発明の第２の実施形態においてＤＮＡ鎖にリンカーを用いてＣｄＳｅ／ＺｎＳ量子ドットが結合されたものを示す略線図である。
【図１１】この発明の第２の実施形態においてＤＮＡ鎖にリンカーを用いてＣｄＳｅ／ＺｎＳ量子ドットが結合されたものを示す略線図である。
【図１２】この発明の第２の実施形態においてＤＮＡ鎖にリンカーを用いてＣｄＳｅ／ＺｎＳ量子ドットが結合されたものを示す略線図である。
【図１３】この発明の第２の実施形態においてＤＮＡ鎖にリンカーを用いてＣｄＳｅ／ＺｎＳ量子ドットが結合されたものを示す略線図である。
【符号の説明】
１・・・ＺｎＳ、２・・・ＣｄＳｅ[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a functional material, a manufacturing method thereof, an electronic device, a manufacturing method thereof, a quantum device, and a manufacturing method thereof, and particularly to synthesis of a high-performance material by a novel technique and its application.
[0002]
[Prior art]
Silicon and magnetic crystalline materials are often used as materials for making electronic devices and storage media that support modern science and technology, and miniaturization and purification technologies can increase device speed and memory capacity. It has been planned. It has also become clear that the characteristic size of these devices and media has reached the order of nanometers (hereinafter simply referred to as “nano”), and problems that could not be considered from the bulk properties up to that point have arisen. It was. Therefore, in addition to the improvement of the prior art, the necessity of a material suitable for the nano-order has been recognized and the search has been vigorously performed. Under such circumstances, materials that are considered to have properties unique to the nano-order are being developed as real substances.
[0003]
Recently, a multiplexed hierarchical structure has been proposed by the present applicant as a material having a higher-order structure that is completely different from conventional crystal-based materials ((1) R. Ugajin, C. Ishimoto, S. Hirata, and Y .Mori: Int. J. Mod. Phys. B, 14, 1825, (2000) (2) R. Ugajin, A. Ishibashi, S. Hirata, C. Ishimoto, and Y. Mori: Phys. Lett. A, 275,467, (2000) (3) R.Ugajin, C.Ishimoto, Y.Kuroki, S.Hirata, and S.Watanabe: Physica A, 292,437, (2001) (4) R.Ugajin: "Anderson Transition in a Multiply -Twisted Helix ", J. Nanosci. Nanotech., 1,227-235, (2001)). Among them, this structure was shown to have completely different physical properties from conventional materials.
[0004]
A multiple spiral structure is defined as an example of a multiplexed hierarchical structure (the above document (1)). The q-fold multi-winding spiral structure is defined as a (q-1) -fold multi-winding spiral that is regarded as a single string and is used as a spiral. If q = 0 is a straight string and q = 1 is a normal helix with a period N, then q multiple-fold helix is N^qWith a period of In this case, assuming that the first one-dimensional string is composed of an element and a connection between them, a multi-helix structure is defined by adding a connection between elements newly generated for multiplexing. . Here, join is one of the following conditions
| Q-p | = 1
| Q-p | = N
qp = N²And mod (p, N) = 0
qp = N^ThreeAnd mod (p, N²) = 1 (1)
qp = N^FourAnd mod (p, N^Three) = 2
:
:
Between elements p and q that satisfy However, mod (a, b) is the remainder when a is divided by b. That is, in addition to the connection between the nearest elements as seen from the one-dimensional chain, all elements are connected to elements separated by N by a single helix, and N elements for each N element.²The combination with the previous element is further N²N per element^ThreeThe connection is determined such that the connection with the previous element is. However, N²The elements coupled with the above long period are different from the elements with different long periods. This structure can be controlled by changing the period N. And, due to the change in the structure, it is possible to greatly change the physical properties that depend on the dimensionality, which has been thought to be determined by the elements that make up the substance so far, the Mott transition (above document (1)) and This was confirmed by examining the ferromagnetic transition (the above document (2)) and the Anderson transition (the above documents (3) and (4)). In addition, generalized structures by adding elements between couplings have also been investigated ((5) R. Ugajin, Y. Watanabe, and Y. Mori: "Multiply-twisted helices of various inter-round couplings", Int J. Mod. Phys. B, 16, 1225-1239, (2002)).
[0005]
The importance of this structure is that physical properties such as magnetism and conductivity can be controlled by changing the structure without changing the substance itself. Therefore, realizing this multiplexed hierarchical structure is a very important issue. As an example so far, a realization method by multiplexing a quantum dot array or carbon nanocoils has been shown, but it is difficult to manufacture a large amount stably at present.
[0006]
In addition, as a material having a structure different from another type of crystal, fractal ((6) BB Mandelbrot: The Fractal Geometry of Nature, (Freeman, San Francisco, 1982) (7) A. Erzan, L. Pietronero, and A. Vespignani: Rev.Mod.Phys., 67,545, (1995)) and dendrimers ((8) S.Hecht and JMJFrechet: "Dendritic Encapsulationof Function: Applying Nature's Site Isolation Principle from Biomimeticsto Materials Science", Angew.Chem Int. Ed., 40, 74-91, (2001) (9) A. Rajca, J. Wongsriratanakul, S. Rajca, and R. Cerny: "A Dendritic Macrocyclic Organic Polyradical with a Very High Spin S = 10" , Angew.Chem.Int.Ed., 37,1229-1232, (1998) (10) D.-L.Jiang and T.Aida: "Morphology-Dependent Photochemical Events in Aryl Ether Dendrimer Porphyrins: Cooperation of Dndron Subunits forSinglet Energy Transition ", J. Am. Chem. Soc., 120, 10895-10901, (1998) (11) M. Enomoto and T. Aida:" Self-Assembly of a Copper-Ligating Dendrimer that Provides a New Non-Heme Metalloprotein Mimic: "Dendrimer Effects" of Stability of the Bis (μ-oxo) dic Opper (III) Core ", J. Am. Chem. Soc., 121, 874-875, (1999)) are also known. Furthermore, the applicant has also proposed a composite fractal structure created by changing the fractal dimension in the middle of growth, and it has been confirmed that new physical properties will emerge through research such as the Anderson transition, the ferromagnetic transition, and the Mott transition. ((12) R.Ugajin, S.Hirata, and Y.Kuroki: "Anderson transition driven by running fractal dimension in a fractal-shaped structure", Physica A, 278,312-326, (2000) (13) R .Ugajin: "Anderson transition in a fractal-based complexes", Physica A, 301,1-16, (2001) (14) R.Ugajin, S.Hirata, and Y.Mori: "Ferromagnetic and Mott transitions modulated byvarying fractal dimensions in fractal-shaped nanostructures ", Int. J. Mod. Phys. B, 15, 2025-2044, (2001)).
[0007]
Biological substances such as DNA (deoxyribonucleic acid), proteins, and nerve cells are known as substances characterized by having a structure different from such crystals. With regard to DNA, research has been conducted on attempts to create complex structures using its selective binding properties, and measurement of electrical properties considering application to molecular wiring in molecular devices ((15) C. Dekker). and MARatner: "Electric properties of DNA", Physics World, 14, (2001) (translated by Kenjiro Miyano: "Does DNA conduct electricity ?, Parity, 17, 4-11 (2002-3)). It has been reported that entangled circles and knots, 1- and 2-dimensional periodic structures, 3-dimensional cubes and the like can be produced by bonding complementary partial sequences in single-stranded DNA (( 16) E. Winfree, F. Liu, LA Wenzler, and NCSeeman: "Design and self-assembly of two dimensional DNA crystal", Nature, 394, 539-544, (1998)). It has been confirmed that charge transfer can be carried out at a distance up to 1. A hole (hole) in DNA is AT (adhesive). N-thymine) is more energetically stable on the GC (guanine-cytosine) base pair than on the G-C pair, so that the AT pair is an energy barrier relative to the GC pair. It is understood that when the distance between the -C pair is short, it is a coherent charge transfer due to the tunnel effect, and when the distance is long, it is a hopping conduction by thermal excitation. Although conduction has not yet been settled, it is thought that it is not a good conductor, so even if a structure such as a multiplexed hierarchical structure can be created by DNA, new physical properties obtained by calculation are expressed. In addition, it is known that when DNA is modified with a gold atom, it is a good conductor, but the structure is also a complex combination of many single-stranded DNAs. That must be created by a process, be made stable is considered difficult.
[0008]
Proteins are known to express their functions by taking a variety of three-dimensional structures such as secondary structures such as α-helix and β-sheet and tertiary structures that are spatial arrangements of them. The relationship with physical properties is also energetically studied. The skeleton responsible for the three-dimensional structure of the protein is composed of a peptide bond main chain formed by dehydration polymerization of an amino group and a carboxyl group. Regarding electrical conduction, oligomers of proline ((17) SSIsied, MYOgawa, and JFWishart: "Peptide-Madiated Intramolecular Electron Transfer: Long-Range Distance Dependence", Chem. Rev., 92, 381-394, (1992)) And α-helix ((18) HBGray and JRWinkler: "Electron tunneling in structurally engineered protein", J. Electroanal. Chem., 438, 43-47, (1997)), the existence of conduction by tunneling is known. Yes. However, it is thought that it is not a good conductor for long-distance conduction across the entire protein molecule. Even if attention is paid to the side chain of each amino acid constituting a protein, some of them have electric charges and polarities, but those constituting a network as a whole and showing conductivity and magnetism are not known. In addition, there has been no report of a protein exhibiting new physical properties related to conductivity and magnetism, which has been characteristic of a multiplexed hierarchical structure.
[0009]
Recently, however, a new method for designing proteins incorporating arbitrary amino acids at arbitrary positions has been developed ((19) I. Hirono, T. Ohtsuki, T. Fujiwara, T. Matsui, T. Yokogawa, T .Okuni, H.Nakayama, K.Takio, T.Yabuki, T.Kigawa, K.Kodama, T.Yokogawa, K.Nishikawa, and S.Yokoyama: "An unnatural base pair for coupled transcription-translation in a cel- free system ", Nature Biotechnol., 20, 177-182, (2002)). Various methods can be used to insert an amino acid having a target side chain at an arbitrary position in a protein, but they constitute a genetic information transcription-translation system capable of generating a target amino acid sequence. Achieved that. The newest point of this method is that it can handle any amino acid including unnatural amino acids and write it as genetic information. Therefore, it becomes possible to stably synthesize a large amount of an artificial protein containing the target unnatural amino acid at an arbitrary position.
[0010]
Two key technologies have been developed to do this. One is the introduction of new base pairs necessary to form codons that specify amino acids, including unnatural amino acids. These base pairs x and y need to be paired with a high probability, but they almost do not form a pair with other natural base pairs A, T (U) (U is uracil), G, and C. Is needed. Therefore, they introduced 2-amino-6- (N, N-dimethylamino) purine as x and prydin-2-one as y ((20) M.Ishikawa.I.Hirano, and S.Yokoyama: "Synthesis of 3- (2-deoxy- β-D-ribofuranosyl) pyridin-2-one and 2-amino-6- (N, N-dimethylamino) -9- (2-deoxy- β-D-ribofuranosyl) purinederivatives for an unnatural base pair ", Tetrahedron Lett. 41, 3931-3934, (2000)), when x is actually embedded in DNA and transcription is performed, RNA (ribonucleic acid) selectively produces y at a position complementary to x. (21) T. Ohtsuki, M. Kimoto, M. Ishikawa, T. Matsui, and S. Yokoyama: "Unnatural base pairs for specific transcription", Proc. Natl. Acad. Sci. USA, 98,4922-4925, (2001)). It is understood that the property that does not pair with a natural base is caused by steric hindrance by 6-dimethylamino contained in x. Therefore, 6- (2-Thienyl) purine (called s), which is a structure that causes steric hindrance more reliably, was introduced in place of x, and it has been confirmed that it actually forms a pair with high precision ((22 ) T.Fujiwara, M.Kimoto, H.Sugiyama, I.Hirano, and S.Yokoyama: "Synthesis of 6- (2-Thienyl) purine Nucleoside Derivatives That Form Unnatural Base Pair with Pyridin-2-one Nucleosides", Bioorg Med. Chem. Lett., 11, 2221-2223, (2001)). In addition, in order to confirm whether the DNA introduced with this new base is correctly used as a template for protein synthesis, first, it binds to 3-chlorotyrosine, which is a non-natural amino acid, to produce tRNA (transfer RNA) having CUx as an anticodon. Subsequently, a new yAG codon introduced into the 32nd codon of the Ras gene is prepared, and an in vitro transcription-translation system containing them is constructed, and 3-chlorotyrosine is actually selectively incorporated. (Reference (19) above).
[0011]
The second is a technique for producing a tRNA capable of selectively recognizing a target non-natural amino acid and a codon including x (s) and y. To show this, among the mutants of Escherichia coli arginyl-tRNA synthetase derived from Escherichia coli, the tRNA that selectively suppresses 3-iodinetyrosine, which is a non-natural amino acid, is more selective than the natural amino acid, tyrosine. ((23) D.Kiga, K.Sakamoto, S.Sato, I.Hirano, and S.Yokoyama: "Shifted positioning of the anticodon nucleotide residues of amber suppressor tRNA species by Escherichiacoli arginyl-tRNA synthetase ", Eur.J.Biochem., 268,6207-6213, (2001)), it was confirmed that 3-iodinetyrosine can be introduced at any position in the in vitro protein synthesis system. . Furthermore, it has succeeded in selectively incorporating non-natural amino acids into cultured cells (the above-mentioned document (23)).
[0012]
On the other hand, it is known that metal nanoparticles such as gold and silver and semiconductor quantum dots can be bound to biomolecules such as DNA and proteins by using an appropriate linker ((24) Christof M. Niemeyer: “Nanoparticles, Proteins, and Nucleic Acids: Biotechnology Meets Materials Science”, Angew. Chem. Ed., 40, 4128-4158, (2001)). In particular, even for DNA strands only, gold nanoparticle binding ((25) W.-L. Shaiu, DL Darson, J. Vesenka, and E. Henderson: Nucleic Acids Res., 21, 99-103, (1993 (26) CAMirkin, RLLestinger, RCMucic, and JJStorhoff: Nature (London), 382, 607-609, (1996) (27) A. Bardea, A. Dagan, I. Ben-Dov, B. Amit, and I. Willner: Chem. Commun., 839-840, (1998) (28) F. Patolsky, KTRanjit, A. Lichtenstein, and I. Willner: Chem. Commun., 1025-1026, (2000) (29 ) RLLestinger, R. Elghanian, G. Viswanadham, and CAMirkin: "Use of a Steroid Cyclic Disulfide Anchor in Constructing Gold Nanoparticle-Oligonucleotide Conjugates", Bioconjugate Chem., 11, 289-291, (2000)), ((30) R.Mahtab, JPRogers, and CJMurphy: J.Am.Chem.Soc., 117,9099-9100, (1995) (31) GPMitchell, CAMirkin, and RLLestinger: "Programmed Assembly of DNA Functionalized Quantum Dots ", J. Am. Chem. Soc., 121, 8122-8123, (1999)). In the case of binding metal, the purpose is to create an array of nanoparticles by considering a single DNA strand as a template and inserting nanoparticles bound to a short complementary strand corresponding to the place to be placed (( 32) X. Yang, LA Wenzler, J. Qi, X. Li, and NCSeeman: J. Am. Chem. Soc., 120, 9779-9786, (1998) and the above literature (16)), their conduction characteristics ((33) E. Braun, Y. Eichen, U. Sivan, and G. Ben-Yoseph: "DNA-templated assembly and electrode attachment of a conducting silver wire", Nature (London), 391, 775) -778, (1998) (34) S.-J.Park, AALazarides, CAMirkin, PWBrazis, CRKannewulf, and RLLestinger: "The Electrical Properties of Gold Nanoparticle Assemblies Linked by DNA", Angew.Chem.Int Ed., 39, 3845-3848, (2000)). Quantum dot binding is mainly intended to be used as a biomolecule marker in vivo ((35) WCWChan and S. Nie: "Quantum Dot Bioconjugates for Ultrasensitive Nonisotopic Detection", Science, 281, 2016 -2018, (1998) (36) M. Bruchez Jr., M. Moronne, P. Gin, S. Weiss, and APAlivisatos: "Semiconductor Nanocrystals as Fluorescent Biological Labels", Science, 281, 2013-2016, (1998 ) (37) H. Mattoussi, JMMauro, G. Goldman, GPAnderson, VC Sundar, FVMikulec, and MGBawendi: "Self-Assembly of CdSe-ZnS Quantum Dot Bioconjugates Using an Engineered Recombinant Protein", J. Am. Chem. Soc. 122, 12142-12150, (2000) (38) Barbera-Guillem: "Functionalized nanocrystals as visual tissue-specific imaging agents, and methods for fluorescence imaging", US Patent 6,333,110 (December 25, 2001) (39) Bawendi , et al .: "Biological applications of quantum dots", US Patent 6,326,144 (December 4, 2001) (40) Barbera-Guillem: "Fluorescence filter cube for fluorescence detection and imaging", US Patent 6,25 2,664 (June 26, 2001) (41) Siiman, et al.,: "Semiconductor nanoparticles for analysis of blood cell populations and methods of making same", US Patent 6,235,540 (May 27, 2001)), improving the hydrophilicity of quantum dots And fluorescence intensity are also important technologies ((42) Bawendi, et al .: “Highly luminescent color-selective nano-crystalline materials”, US Patent 6,322,901 (November 20, 2001) (43) Bawendi, et al. .: "Water-soluble fluorescent semiconductor nanocrystals", US Patent 6,319,426 (November20,2001) (44) Weise, et al.:"Semiconductor nanocrystal probes for biological applications and process for making and using such probes ", US Patent 6,207,392 (March27 (2001) (45) Castro, et al .: "Functionalized nanocrystals and their use in detection systems", US Patent 6,114,038 (September 5, 2000)).
[0013]
It is known that DNA strands usually have a double helix structure by binding two DNA strands having complementary base sequences. Recently, however, methods have been found to create intertwined rings and knots, 1- and 2-dimensional periodic structures, 3-dimensional cubes, etc. by joining complementary subsequences to multiple DNA strands. ((46) Nadrian C. Seeman: “Nucleic Acid Nanostructures and Topology”, Angew. Chem. Int. Ed., 37, 3220-3238, (1998) (47) THLaBean, H. Yan, J. Kopatsch, F .Liu, E. Winfree, JHReif, and NCSeeman: "Construction, Analysis, Litigation, and Self-Assembly of DNA Triple Crossover Complexes", J. Am. Chem. Soc., 122, 1848-1860, (2000) ). These technologies are molecular devices that switch between DNA strands with different shapes and topologies by chemical procedures ((48) PJKuekes, RSWilliams, and JRHeath: "Molecular-Wire Crossbar Interconnect (MWCI) for Signal Routing and Communications ", US Patent 6,314,019, (November6,2001) (49) PJKuekes, RSWilliams, and JRHeath:" Molecular Wire Crossbar Interconnect Memory ", US Patent 6,128,214, (October3, 2000)) and DNA strands DNA computations that perform calculations based on the bond between each other ((50) LMAdleman: "Molecular computation of solutions to combinatorial problems", Science, 226, 1012-1024, (1994) (51) RJLipton: "Using DNA to solve NP- complete problems ", Science, 268,542-545, (1995)) ((52) C.Mao, THLaBean, JHReif, and NCSeeman:" Logical computation usingalgorithmic self-assembly of DNA triple-crossover molecules ", Nature (London), 407,493-496, (2000) (53) H.Yan, X.Zhang, Z.Shen, and NCSeeman:" A robust DNA mechanical device controlled by hybridizat ion topology ", Nature (London), 415, 62-65, (2002)).
[0014]
[Problems to be solved by the invention]
An object of the present invention is to solve the above-described problems of the prior art in realizing a novel structure such as a multiplexed hierarchical structure.
That is, the problem to be solved by the present invention is to provide a functional material capable of obtaining a large amount of functional materials exhibiting abundant physical properties at a low cost and a method for producing the same.
Another problem to be solved by the present invention is to provide an electronic device using the functional material described above, a manufacturing method thereof, a quantum device, and a manufacturing method thereof.
[0015]
[Means for Solving the Problems]
The present inventor believes that it is most effective to use a molecular biological method in order to realize a novel structure such as a multiplexed hierarchical structure or a fractal structure previously proposed by the present applicant in large quantities at low cost. Various ideas were considered. As a result, a method for realizing a peptide-binding chain incorporating an unnatural amino acid using an expanded genetic information transcription-translation system including unnatural base pairs, or a plurality of partially complementary chains. The method realized by the structure which combined the polynucleotide chain of was considered. More specifically, for the former, unnatural amino acids having side chains according to the purpose are placed in an appropriate three-dimensional structure using a method of biosynthesis of unnatural proteins, and physical properties are expressed in the side chains. For example, by combining nanostructures such as semiconductor quantum dots as necessary elements, it is possible to stably realize a large amount of materials having a novel structure such as a multiplexed hierarchical structure or a fractal structure. It is done. As for the latter, a nanostructure for expressing physical properties is bound to an appropriate place on the basis of an assembly of a plurality of DNA strands whose partial strands are complementary strands.
[0016]
Up to now, there is a method of using “self-organization” as a technique for giving a structure in some sense, but it can be said that the above method goes beyond this self-organization technique. That is, in self-organization, materials that can have a complicated structure are determined, and it is currently impossible to freely arrange materials of interest (such as nanoparticles) as physical properties. On the other hand, here, the target nanoparticles and the like can be structured by the force of biomolecules, which are typically self-organized and self-structured materials.
The present invention has been devised based on the above examination by the present inventors.
[0017]
That is, in order to solve the above problem, the first invention of the present invention is:
Including a peptide bond chain consisting of an amino acid sequence in which amino acids having side chains to which a microstructure is selectively bonded are incorporated at predetermined positions;
The spatial structure of one or more microstructures is determined by the three-dimensional structure of the peptide bond chain
It is a functional material characterized by this.
[0018]
The second invention of this invention is:
Incorporating an amino acid having a side chain to which a microstructure is selectively bonded at a predetermined position of a peptide bond chain consisting of an amino acid sequence,
The arrangement of one or more microstructures in the space is determined by allowing the peptide bond chain to take a predetermined three-dimensional structure.
This is a method for producing a functional material.
[0019]
The third invention of the present invention is:
Comprising a plurality of polynucleotide strands comprising a polynucleotide strand associated with a microstructure;
In the space of one or a plurality of microstructures by a three-dimensional structure taken by a pair of polynucleotide strands including a polynucleotide strand bound to at least a microstructure in a plurality of polynucleotide strands joined by complementary base pairs Placement is decided
It is a functional material characterized by this.
[0020]
The fourth invention of the present invention is:
Preparing a plurality of polynucleotide chains including a polynucleotide chain bound to a microstructure;
In a plurality of polynucleotide chains, a pair of polynucleotide chains including at least a polynucleotide chain bound to a microstructure are joined by complementary base pairs to obtain a predetermined three-dimensional structure, and one or a plurality of microstructures Decided the arrangement in the body space
This is a method for producing a functional material.
[0021]
The fifth invention of the present invention is:
Arrangement in space of one or a plurality of microstructures, including a peptide bond chain consisting of an amino acid sequence in which amino acids having side chains to which the microstructures are selectively bonded are incorporated at predetermined positions, depending on the three-dimensional structure taken by the peptide bond chains Using functional materials for which
This is an electronic device.
[0022]
The sixth invention of the present invention is:
Incorporating an amino acid having a side chain to which a microstructure is selectively bonded at a predetermined position of a peptide bond chain consisting of an amino acid sequence,
A step of producing a functional material by determining the arrangement of one or a plurality of microstructures in a space by causing a peptide bond chain to take a predetermined three-dimensional structure;
This is a method for manufacturing an electronic device.
[0023]
The seventh invention of the present invention is:
Comprising a plurality of polynucleotide strands comprising a polynucleotide strand associated with a microstructure;
In the space of one or a plurality of microstructures by a three-dimensional structure taken by a pair of polynucleotide strands including a polynucleotide strand bound to at least a microstructure in a plurality of polynucleotide strands joined by complementary base pairs Using functional materials whose arrangement is determined
This is an electronic device.
[0024]
The eighth invention of the present invention is:
Preparing a plurality of polynucleotide chains including a polynucleotide chain bound to a microstructure;
In a plurality of polynucleotide chains, a pair of polynucleotide chains including at least a polynucleotide chain bound to a microstructure are joined by complementary base pairs to obtain a predetermined three-dimensional structure, and one or a plurality of microstructures It has a process of manufacturing functional materials by determining the arrangement in the body space
This is a method for manufacturing an electronic device.
[0025]
The ninth aspect of the present invention is:
Arrangement in space of one or a plurality of microstructures, including a peptide bond chain consisting of an amino acid sequence in which amino acids having side chains to which the microstructures are selectively bonded are incorporated at predetermined positions, depending on the three-dimensional structure taken by the peptide bond chains Using functional materials for which
It is a quantum device characterized by this.
[0026]
The tenth aspect of the present invention is:
Incorporating an amino acid having a side chain to which a microstructure is selectively bonded at a predetermined position of a peptide bond chain consisting of an amino acid sequence,
A step of producing a functional material by determining the arrangement of one or a plurality of microstructures in a space by causing a peptide bond chain to take a predetermined three-dimensional structure;
This is a method of manufacturing a quantum device.
[0027]
The eleventh aspect of the present invention is:
Comprising a plurality of polynucleotide strands comprising a polynucleotide strand associated with a microstructure;
In the space of one or a plurality of microstructures by a three-dimensional structure taken by a pair of polynucleotide strands including a polynucleotide strand bound to at least a microstructure in a plurality of polynucleotide strands joined by complementary base pairs Using functional materials whose arrangement is determined
It is a quantum device characterized by this.
[0028]
The twelfth aspect of the present invention is
Preparing a plurality of polynucleotide chains including a polynucleotide chain bound to a microstructure;
In a plurality of polynucleotide chains, a pair of polynucleotide chains including at least a polynucleotide chain bound to a microstructure are joined by complementary base pairs to obtain a predetermined three-dimensional structure, and one or a plurality of microstructures It has a process of manufacturing functional materials by determining the arrangement in the body space
This is a method of manufacturing a quantum device.
[0029]
In this invention, the functional material typically has a plurality of microstructures, and at least two of these microstructures are bonded to each other, or the plurality of microstructures are bonded to each other. . Here, the term “bond” includes both a case where the microstructure is in direct contact and a case where the microstructure is not in direct contact but is bonded by the quantum mechanical tunnel effect. The plurality of microstructures can take various arrangements, and specifically are arranged to take a one-dimensional chain shape, a spiral shape, a branched structure, a fractal structure, a multiplexed hierarchical structure, and the like. In addition, as the amino acid having a side chain to which the microstructure is selectively bound, an unnatural amino acid, in other words, an artificial amino acid is used. The microstructure is generally a nanostructure, specifically, a quantum dot, particularly a semiconductor quantum dot. For example, the microstructure is a semiconductor quantum dot made of CdSe covered with ZnS. An example of a side chain to which a microstructure is selectively bonded is mercaptoacetic acid. This side chain is particularly suitably used for bonding semiconductor quantum dots made of CdSe covered with ZnS.
[0030]
The functional material is most simply composed of a peptide bond chain or a polynucleotide chain, but if necessary, other materials may be combined in the required mixing ratio and distribution depending on the function to be provided. Good. Examples of electronic devices include magnetic elements using ferromagnetism and switching elements using metal-insulator transition. An example of a quantum device is a quantum computing device. Note that a quantum device may be viewed as an electronic device.
[0031]
According to the present invention configured as described above, a peptide bond chain consisting of an amino acid sequence in which an amino acid having a side chain to which a microstructure is selectively bound is incorporated at a predetermined position, or a polynucleotide chain bound to the microstructure. A plurality of polynucleotide chains containing can be produced in large quantities at low cost by a biosynthetic technique.
[0032]
DETAILED DESCRIPTION OF THE INVENTION
Embodiments of the present invention will be described below.
First embodiment
In the first embodiment, at least a peptide bond chain consisting of an amino acid sequence in which amino acids having side chains to which a microstructure is selectively bonded is incorporated at a predetermined position is included. Alternatively, a functional material whose arrangement in a space of a plurality of microstructures is determined will be described.
[0033]
(1) Amino acids that bind to quantum dots
Here, quantum dots (semiconductor nanocrystals) are taken as microstructures constituting the three-dimensional structure. Specifically, as shown in FIG. 1, a quantum dot composed of CdSe2 covered with ZnS1, that is, a CdSe / ZnS quantum dot is considered. Since the energy gap of the semiconductor CdSe2 is about 1.7 eV and the energy gap of the semiconductor ZnS1 is about 3.8 eV, the potential structure of this CdSe / ZnS quantum dot is a well-type potential having an energy difference of about 1.1 eV. (FIG. 2). It can also be seen that when two CdSe / ZnS quantum dots are sufficiently close to each other, as shown in FIG. 3, electrons doped by the tunnel effect can be conducted. The degree to which CdSe / ZnS quantum dots bonded to amino acids are close to each other depends on the size of the CdSe / ZnS quantum dots and the relationship of the configuration of amino acids to which the CdSe / ZnS quantum dots bind. Since the CdSe / ZnS quantum dots can be produced in a desired size from about 1 nm to several tens of nm, it is necessary to take a size necessary for several kinds of designs described later. it can. Several methods for binding CdSe / ZnS quantum dots to biomolecules are known (the above references (36) (37) (42) (43)). In addition, application as a marker for examining the function of biomolecules in vivo has been reported (the above-mentioned documents (38) (39) (40) (41) (44) (45)). Here, among them, mercaptoacetic acid-S-CH₂Bonding by —CO—NH— (the above document (35)) is performed. In this case, S of mercaptoacetic acid is bonded to ZnS1 on the outer periphery of the CdSe / ZnS quantum dot, and NH is bonded to an amino acid. Therefore, here, HS-CH is used as the side chain.₂An unnatural amino acid (referred to herein as Lnk) with —CO—NH— is prepared and an artificial protein is synthesized that is incorporated at the appropriate place in the amino acid sequence. Then, after the artificial protein is synthesized and has a three-dimensional structure, CdSe / ZnS quantum dots are bound to the protein by chemical means (the above-mentioned document (35)). At that time, the CdSe / ZnS quantum dots are surrounded by -S-CH as shown in FIG.₂Since it is covered with COOH, which becomes an obstacle to bonding the CdSe / ZnS quantum dots, the outer periphery of the CdSe / ZnS quantum dots is covered with -S-CH₂The part of COOH other than the bond with amino acid is chemically removed. By doing so, a coupled quantum dot having a desired three-dimensional structure can be constructed.
[0034]
(2) Amino acid recognition
When a new unnatural amino acid is introduced into a protein, it is necessary for the tRNA to selectively recognize the amino acid and have an anticodon corresponding to the codon specifying that amino acid. In particular, the corresponding aminoacyl-tRNA synthetase (aaRS) is required for tRNA to be correctly associated with the target amino acid. That is, it is understood that a new aaRS needs to be produced in order to introduce an unnatural amino acid.
[0035]
Since it has already been demonstrated that such operations are possible in principle (reference (23) above), it is also designed for non-natural amino acids with side chains that consider conductivity and magnetism. It can be considered possible.
[0036]
Therefore, here, the non-natural base pair s, y introduced by Yokoyama et al. In order to produce DNA and RNA encoding Lnk (the above-mentioned document (22)) is introduced. Then, yAG (A and G are natural base pairs adenine and guanine) is used as a codon encoding Lnk, and CUs is used as an anticodon of tRNA that recognizes it. It has been demonstrated that these can be incorporated at any position (the above-mentioned document (19)).
[0037]
(3) One-dimensional chain structure
First, a quantum dot having a basic one-dimensional chain coupling structure for constructing a structure is specifically manufactured. This system is simple but has theoretically interesting results ((54) R. Ugajin: “Hubbard gap tunneling in quantum dot chain: an investigation using absorption spectra”, Phys. Rev. Lett. 80, 572-575. (1998) (55) R. Ugajin: “Hubbard-gap tunneling in disordered quantum-dot chains”, Phys. Rev. B59, 4952-4960, (1999)). Here, influenza virus hemagglutinin is taken up as a representative protein having a long α-helix, and a part of its amino acid sequence is changed to Lnk, which is an unnatural amino acid. Hereinafter, the abbreviations in Table 1 are used for proteins.
[0038]

[0039]
The three-dimensional structure of this protein has been determined by X-ray structural analysis by Bullough et al. ((56) PABullough, FMHughson, JJSkehel, and DCWiley: "Structure of influenza haemagglutinin at the Ph of membrane fusion", Nature (London), 371, 37-43, (1994)), and the information is registered in Protein Data Bank (PDB, http://www.rcsb.org/pdb/) (Registration ID: 1HTM). This protein contains three long (about 10 nm) α-helices. Here, a single α-helix composed of 64 residues from the 41st residue Thr to the 104th residue Asn is taken up, and a part of the amino acids is considered to be changed to Lnk.
[0040]
The α-helix is composed of 3.6 residues per turn, and the pitch is 0.54 nm. Therefore, when the amino acid is changed to Lnk every 7 residues and a CdSe / ZnS quantum dot having a diameter of about 1 nm is bonded to the side chain, the CdSe / ZnS quantum dot is close to each other as shown in FIG. It can be seen that the structure is arranged in a line. In this case, nine residues can be changed, specifically (42: Gln), (49: Asn), (56: Ile), (63: Phe), (70: Phe), All amino acid residues (77: Ile), (84: Val), (91: Leu), and (98: Leu) are changed to Lnk. The α-helix is a relatively stable structure, and it can be expected to maintain the structure with a small number of residue changes.
[0041]
Based on this design, a combined quantum dot having a one-dimensional chain structure can be constructed by using the biosynthesis by transcription-translation and the method of combining side chains and quantum dots.
[0042]
(4) Spiral structure
Next, a coupled quantum dot with a helical structure is constructed. Take the Hc fragment of lactose-binding tetanus toxin as the underlying protein. The ID of the PDB is 1DLL. The conformation of this protein was determined by Emsley et al. ((57) P. Emsley, C. Fotinou, I. Black, NFFairweather, IGCharles, C. Watts, E. Wewitt, and NWIsaacs: "The structures of the H (C) fragment of tetanus toxin with carbohydrate subunit complexes provide insight into canglioside binding ", J. Biol. Chem. 275, 8889, (2000)). This protein takes a jellyroll barrel, one of the typical secondary structure motifs. This is shown in the boxed area in FIG. This is a structure in which 17 stable secondary structure β-strands are gathered to form a barrel, which is considered relatively stable with respect to the replacement of a small number of amino acids. This secondary structure motif is comprised from the 885th residue to the 1092nd residue. The number of β-strands of interest is 15, and the numbers given to the secondary structures in the order in which they appear in the direction from the N-terminal to the C-terminal of the amino acid sequence are 4 (885-888), 5 (889-892), 7 (895, respectively. -898), 9 (905-908), 15 (933-936), 21 (950-957), 25 (973-978), 27 (990-996), 29 (999-1005), 31 (1011- 1017), 33 (1032-1038), 35 (1043-1048), 37 (1051-1057), 39 (1069-1075), 41 (1084-1092) (the numbers in parentheses are the residues constituting the strand) It is.
[0043]
As shown in FIG. 5, in order to arrange quantum dots in a spiral shape, starting from 4 β-strands, 4 → 41 → 21 → 33 → 35 → 37 → 31 → 29 → 27 → 25 → 39 → 15 → 9 → 7 → 5 →41→21→33→35→37→31→29→27→25→39Consider building a helical structure such that the underline represents the strand that passes through the second turn of the helix. Therefore, in each strand, 4 (886: Ile), 41 (1085: Ser, 1091: Ile), 21 (951: Thr, 955: Trp), 33 (1033: Phe, 1037: Thr), 35 (1044: Ala) , 1048: Ile), 37 (1052: Leu, 1056: Ala), 31 (1012: Arg, 1016: Phe), 29 (1000: Leu, 1004: Leu), 27 (991: Trp, 995: Leu), 25 (974: Tyr, 978: Ser), 39 (1070: Ile, 1074: Leu), 15 (934: Ile), 9 (906: Val), 7 (896: Ile), 5 (890: Asp), An amino acid sequence in which each residue is changed to Lnk is designed.
[0044]
From this design, a coupled quantum dot system having a helical structure can be produced by biosynthesis and coupling of quantum dots in the same manner as described above. By using this method to place coupled quantum dots with a helical structure around quantum wires, a device with a new function ((58) R.Ugajin: "Charge transfer device", US Patent 5,828,090 (October27 , 1998)) can also be realized.
[0045]
(5) Branch structure
Next, a branch structure is constructed. As the original protein, a DD-peptidase enzyme acting on penicillin is taken. This conformation is described by Kelly et al. ((59) JAKelly, JRKnox, H. Zhao, JMFrere, and JMGhuysen: "The refined crystallographic structure of a DD-peptidase penicillin-target enzyme at 1.6Å resolution", J. Mol. Biol., 254, 223, (1995)) (PDB ID: 3PTE). The numbers assigned to the secondary structure in the same manner as described above, β (54 (317-323), 4 (25-32), 6 (35-42) (numbers of residues constituting the strands in parentheses) -Consider a strand and design a structure with one branch at 54-4 and two branches at 4-6 (FIG. 6).
[0046]
Specifically, in each strand, each residue of 54 (320: Thr), 4 (26: Ala, 30: Val), 6 (35: Thr, 37: His, 39: Leu, 41: Glu) Each amino acid sequence changed to Lnk is designed.
Thus, a coupled quantum dot having a branched structure can be produced by the same procedure as described above.
[0047]
(6) Higher order structure
A typical higher-order structure, such as a multiplexed hierarchical structure or fractal structure, can be configured by combining the three basic structures up to the previous section, a spiral structure, a branched structure, and a one-dimensional chain structure. Then, it can be seen that in the multi-winding spiral structure, it is only necessary to add a branch to both elements to be coupled as distant bonds based on the spiral structure and to couple them in a one-dimensional chain. A fractal structure can also be realized by combining a branch and a one-dimensional chain in a self-similar manner. Therefore, it can be seen that these higher-order structures can also be produced by the technique here.
[0048]
Second embodiment
The second embodiment includes a plurality of polynucleotide chains including a polynucleotide chain bound to a microstructure, and at least a pair of the plurality of polynucleotide chains including a polynucleotide chain bound to the microstructure. A functional material in which the arrangement of one or a plurality of microstructures in the space is determined by the three-dimensional structure taken by binding the polynucleotide strands by complementary base pairs will be described.
[0049]
(1) Bonding of DNA chain and quantum dot
Here, it is considered that CdSe / ZnS quantum dots are bonded to the DNA strand 4 as shown in FIG. The details of the CdSe / ZnS quantum dots are as described in the first embodiment. In this case, -S- (CH as a linker₂)₆By using-, CdSe / ZnS quantum dots can be bound to the ends of DNA strands (the above-mentioned document (31)).
[0050]
In order to bond a CdSe / ZnS quantum dot to an arbitrary position of the DNA strand 4, it is utilized that the DNA strand 4 is paired with a DNA strand having a complementary base sequence. One long DNA strand is prepared, and a short DNA strand having a complementary base sequence at the target position is brought. Then, as shown in FIG. 8, a procedure may be used in which CdSe / ZnS quantum dots are bonded to the ends of the short DNA strands using the linker described above and bonded to the long DNA strands. It can also be seen that by changing the length and number of the short DNA strands, any number of CdSe / ZnS quantum dots can be placed at any position in the base sequence of the long DNA strand.
[0051]
(2) One-dimensional chain structure
First, a quantum dot having a basic one-dimensional chain coupling structure for constructing a structure is specifically manufactured. As already mentioned, this system is simple, but theoretically interesting results have been obtained (the above documents (54) (55)).
[0052]
Consider a double helix consisting of two normal complementary DNA strands. It is known that DNA molecules have a structure called B-type mainly in cells ((60) T.A.Brown: "Genomes" (BIOS Scientific Publishers, Oxford, 1999)). In this structure, the diameter of the helix is 2.37 nm, which is one pitch (3.4 nm) with 10 base pairs. The typical size of the CdSe / ZnS quantum dots used here is 1 nm to several tens of nm. Therefore, a long DNA strand having a length of 100 bases is taken, and a short DNA strand having a length of 10 bases and 10 CdSe / ZnS quantum dots bonded to the 5′-end thereof are taken. As shown in FIG. 9, it is assumed here that each short DNA strand has an appropriate base sequence, and can be arranged in a bond with a base pair in a complementary manner to the long DNA strand.
[0053]
It can be seen that the double chain thus formed has a 10-cycle helical structure, and the CdSe / ZnS quantum dots bonded as described above have a one-dimensional chain structure as shown in FIG. At this time, since the distance between the centers of CdSe / ZnS quantum dots is about 3.4 nm, it can be seen that the CdSe / ZnS quantum dots can be combined within a typical size range.
[0054]
(3) Spiral structure
Next, consider placing CdSe / ZnS quantum dots in a helical structure. Therefore, under the same conditions as in (2) above, a long DNA strand having a length of 110 bases was taken, and a short DNA strand having a length of 11 bases was bound with a CdSe / ZnS quantum dot at its 5'-end. I will take 10 of them.
[0055]
When the double chain thus formed has a 11-cycle helical structure, it can be seen that the CdSe / ZnS quantum dots bonded as described above have a 1-cycle helical structure as shown in FIG. At this time, the distance between the centers of the CdSe / ZnS quantum dots is about 4.03 nm, and in this case, the CdSe / ZnS quantum dots can be combined within a typical size range of CdSe / ZnS quantum dots.
[0056]
It can also be seen that if CdSe / ZnS quantum dots are bonded to each DNA strand of one base length, the distance between the centers of the quantum dots is about 1.53 nm.
[0057]
Furthermore, a helical structure can be designed in the same manner for the type A which is a three-dimensional structure of different DNA molecules (helical diameter 2.55 nm, pitch is 11 base pairs and 3.2 nm).
[0058]
(4) Branch structure
Next, a branch structure is constructed. Here, a branched structure is formed by connecting CdSe / ZnS quantum dots bonded to the tips of two-branched DNA molecules and connecting them together.
[0059]
First, as shown in FIG. 12, a DNA molecule having two branches is designed. In addition to the two DNA strands necessary for constructing a normal double helix, another DNA strand is prepared. These DNA strands are named A, B, and C. In addition, each DNA strand is divided into two parts, each of which is A (B, C)₁, A (B, C)₂It shall be expressed as It can be seen that the following conditions must be satisfied in order for these three DNA strands to bond partially complementary strands to form one structure successfully.
[0060]
A₁= B₂bar
B₁= C₂Bar (2)
C₁= A₂bar
Here, X bar represents a complementary strand of the partial chain X. Specifically, it is assumed that a double helix having a length of 10 base pairs each appears from the branched portion. If a CdSe / ZnS quantum dot is bonded to the tip, the distance between the centers of the quantum dots is about 5.88 nm, which is a designable size. Further, in practice, in order to selectively bind DNA strands, a certain partial strand is designed so as not to have a complementary strand relationship other than the target partial strand.
[0061]
If one CdSe / ZnS quantum dot is bonded to 10 bases when bibranched DNA is produced by the above-described method, a bifurcated structure of CdSe / ZnS quantum dots can be produced.
[0062]
In addition, seven bifurcated DNAs having CdSe / ZnS quantum dots bound thereto were prepared and described in Zhang and Seeman ((61) J. Am. Chem. Soc., 114, 2656-2663, (1992)). By combining them as shown in FIG. 13, a three-stage bifurcated structure can be produced.
[0063]
In this method, only a planar branch structure can be constructed. However, since a three-branch and four-branch structure other than two branches can actually be constructed, they are combined and the spiral structure described in the previous section. It can be seen that a branching structure in a three-dimensional space can also be configured by appropriately introducing a halfway. Thereby, a fractal structure can also be produced.
[0064]
(5) Multiple winding spiral structure
As described in the section of the prior art, the multi-winding spiral structure is configured by taking long-period inter-element coupling in addition to the basic one-dimensional chain and the spiral structure. Therefore, if the bifurcated structure of (4) above is introduced with a long period and the branches are connected by a one-dimensional chain structure based on the helical structure configured in (3) above, a double-wound helical structure Can be configured. Similarly, a higher-order long-period structure can be introduced, and a general multi-winding spiral structure can also be configured.
[0065]
(6) Application
By using this technique, a coupled quantum dot in which semiconductor quantum dots are arranged in a spatially structured state can be produced. For example, it is known that a device having a novel function can be realized by arranging coupled quantum dots having a helical structure around a quantum wire (the above-mentioned document (39)).
[0066]
Also, coupled quantum dots can be calculated by quantum computation ((62) P. Benioff: "The Computer as a Physical System: A Microscopic Quantum Mechanical Hamiltonian Model of Computers as Represented by Turing Machines", J. Stat. Phys., 22, 563-591, (1980) (63) R.Feynman: "Quantum Mechanical Computers", Opt.News, 11,11-20, (1985) (64) D.Deutsch: "Quantum Theory, the Church-Turing Principle, and the Universal Quantum Computer ", Proc.Roy.Soc.London, Ser.A400,97-117, (1985) (65) MANielsen and ILChuang:" Quantum Computation and Quantum Information ", (Cambridge University Press, Cambridge, UK, 2000) (66) A. Barenco, D. Deutsch, and A. Ekert: Phys. Rev. Lett., 74, 4083, (1995) (67) D .Loss and DPDiVincenzo: "Quantum Computation with Quantum Dots", Phys.Rev.A57,120, (1998) (68) VNGolvach and D.Loss: "Electron Spins in Artificial Atoms and Molecules for Quantum Computing", Special Issue of Semiconductor Science and Technology, "Semiconductor Spintronics", ed.H. Ohno, (2002)). By using the technique described here, it is possible to construct a coupled quantum dot having not only a one-dimensional coupling but also a higher-order coupling structure, so that a conventionally known quantum algorithm ((69) D. Deutsch and R.Jozsa: "Rapid Solution of Problems by Quantum Computation", Proc.Roy.Soc.London, A439,553-558, (1992) (70) PWShor: "Algorithms for Quantum Computation: Discrete Logarithms and Factoring" , Proceedings of the 35th Annual Symposium on Foundation of Computer Science, 124-134, (1994) (71) LKGrover: "A fast quantum mechanical algorithm for database search", Proceedings of the 28th Annual ACM Symposium on the Theory of Computing, 212-219, (1996)), and the realization of a completely new quantum algorithm that takes advantage of the geometrical nature of the coupling can be expected.
[0067]
Although the embodiments of the present invention have been specifically described above, the present invention is not limited to the above-described embodiments, and various modifications based on the technical idea of the present invention are possible.
[0068]
For example, the numerical values, materials, structures, shapes, and the like given in the above-described embodiments are merely examples, and different values, materials, structures, shapes, etc. may be used as necessary.
[0069]
【The invention's effect】
As described above, according to the present invention, one or a plurality of microscopic structures are formed by a three-dimensional structure taken by a peptide-binding chain composed of an amino acid sequence in which amino acids having side chains to which microstructures selectively bind are incorporated at predetermined positions. A plurality of polynucleotide chains including a polynucleotide chain that determines the arrangement of the structure in the space or is bound to the microstructure, and at least a polynucleotide chain that is bound to the microstructure in the plurality of polynucleotide chains. Since the arrangement of one or a plurality of microstructures in the space is determined by the three-dimensional structure taken by combining a pair of polynucleotide strands with complementary base pairs, a large amount of functional materials that express abundant physical properties at low cost This functional material can be used to realize various highly functional electronic devices or quantum devices. That.
[Brief description of the drawings]
FIG. 1 is a schematic diagram showing the configuration of CdSe / ZnS quantum dots used in the first embodiment of the present invention.
FIG. 2 is a schematic diagram showing an energy band of a CdSe / ZnS quantum dot used in the first embodiment of the present invention.
FIG. 3 is a schematic diagram for explaining a tunnel effect when two CdSe / ZnS quantum dots are close to each other in the first embodiment of the present invention.
FIG. 4 is a schematic diagram showing a combination of CdSe / ZnS quantum dots every 7 amino acid residues of an α-helix in the first embodiment of the present invention.
FIG. 5 is a schematic diagram showing a combination of CdSe / ZnS quantum dots spirally attached to a jelly roll barrel in the first embodiment of the present invention.
FIG. 6 is a schematic diagram showing a structure in which CdSe / ZnS quantum dots are combined in a spiral with a jelly roll barrel in the first embodiment of the present invention.
FIG. 7 is a schematic diagram showing a state in which a DNA chain is bonded to a CdSe / ZnS quantum dot in the second embodiment of the present invention.
FIG. 8 is a schematic diagram showing a CdSe / ZnS quantum dot bonded to a DNA strand using a linker in the second embodiment of the present invention.
FIG. 9 is a schematic diagram showing a CdSe / ZnS quantum dot bonded to a DNA strand using a linker in the second embodiment of the present invention.
FIG. 10 is a schematic diagram showing a CdSe / ZnS quantum dot bonded to a DNA strand using a linker in the second embodiment of the present invention.
FIG. 11 is a schematic diagram showing a CdSe / ZnS quantum dot bonded to a DNA strand using a linker in the second embodiment of the present invention.
FIG. 12 is a schematic diagram showing a CdSe / ZnS quantum dot bonded to a DNA strand using a linker in the second embodiment of the present invention.
FIG. 13 is a schematic diagram showing a CdSe / ZnS quantum dot bonded to a DNA strand using a linker in the second embodiment of the present invention.
[Explanation of symbols]
1 ... ZnS, 2 ... CdSe

Claims (17)

The α-helix residue in the protein containing an α-helix is changed to an unnatural amino acid having a side chain to which a semiconductor quantum dot selectively binds every 7 residues, and the semiconductor quantum dot is changed to the side chain. An electronic device using a combination of these. The electronic device according to claim 1, wherein the semiconductor quantum dot has a diameter of about 1 nm. 3. The electronic device according to claim 1, wherein the semiconductor quantum dots are made of CdSe covered with ZnS. The electronic device according to claim 1, wherein the side chain is mercaptoacetic acid. 3. The semiconductor quantum dot is made of CdSe covered with ZnS, the side chain is mercaptoacetic acid, and the ZnS of the semiconductor quantum dot is bonded to S of the mercaptoacetic acid. Electronic equipment. The electronic device according to any one of claims 1 to 5, wherein the protein is influenza virus hemagglutinin. The 42nd, 49th, 56th, 63rd, 70th, 77th, 84th, 91st and 98th residues of said influenza virus hemagglutinin are changed to said unnatural amino acid. 6. The electronic device according to 6. 886th, 1085th, 1091th, 951th, 955th, 1033th, 1037th, 1044th, 1048th, 1052, 1056th, 1012th, 1016th, 1000th of the Hc fragment of lactose-binding tetanus toxin, 1004th, 991st, 995th, 974th, 978th, 070th, 1074th, 934th, 934th, 906th, 896th and 890th residues are side chains to which semiconductor quantum dots are selectively bonded. An electronic device using an unnatural amino acid having the semiconductor quantum dot bonded to the side chain. The electronic device according to claim 8, wherein the semiconductor quantum dot has a diameter of about 1 nm. The electronic device according to claim 8 or 9, wherein the semiconductor quantum dots are made of CdSe covered with ZnS. The electronic device according to claim 8, wherein the side chain is mercaptoacetic acid. The semiconductor quantum dot is made of CdSe covered with ZnS, the side chain is mercaptoacetic acid, and the ZnS of the semiconductor quantum dot is bonded to S of the mercaptoacetic acid. Electronic equipment. The 320th, 26th, 30th, 35th, 37th, 39th and 41st residues of the DD-peptidase enzyme are changed to unnatural amino acids having side chains to which semiconductor quantum dots are selectively bound. An electronic device using the semiconductor quantum dot bonded to the side chain. The electronic device according to claim 13, wherein the semiconductor quantum dot has a diameter of about 1 nm. 15. The electronic device according to claim 13, wherein the semiconductor quantum dot is made of CdSe covered with ZnS. The electronic device according to claim 13, wherein the side chain is mercaptoacetic acid. The semiconductor quantum dot is made of CdSe covered with ZnS, the side chain is mercaptoacetic acid, and the ZnS of the semiconductor quantum dot is bonded to S of the mercaptoacetic acid. Electronic equipment.

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