高分子 Vol.63 No.10
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特集 高分子のリプログラミング
展望 COVER STORY: Highlight Reviews
Ribosomal Synthesis of Functional Macrocyclic Polypeptides and RaPID Discovery of Bioactive Polypeptides
菅 裕明・吉冨 徹・長野 正展
Hiroaki SUGA, Toru YOSHITOMI, Masanobu NAGANO
<要旨> 非タンパク質性アミノ酸を含む一兆種類を超えるポリペプチドの中から、標的タンパク質と高度選択的に結合する機能性ポリペプチドを迅速に探索する基盤技術、RaPIDシステムが開発された。ここでは、RaPIDシステムとそれを駆使して発見された機能性大環状ポリペプチドの例を紹介する。
Keywords: Genetic Code Reprogramming / Flexizyme / Aminoacylation Ribozymes / Rebosomal Translation / Macrocyclic Polypeptide / FIT System / Nonnatural Amino Acids / RaPID System
Precision Control of Monomer Sequences in Vinyl Copolymers
佐藤 浩太郎・上垣外 正己
<要旨> 重合反応におけるモノマー配列制御は、合成高分子を単純なバルク材料としてではなく、その高次構造形成により一つの大きな分子として機能させる夢へとつながる。とくにビニルポリマーのモノマー配列制御は高分子合成における究極の課題であるが、重合技術の発展により、共重合や組成の新たな制御手法が試みられてきている。本稿では、ラジカル重合を中心としたモノマー配列制御について、近年のさまざまな研究例を紹介する。
Keywords: Monomer Sequnece / Living Polymerization / Radical Polymerization / Vinyl Polymer / Copolymerization / Atom Transfer Radical Addition / Alternating Copolymerization / Metathesis Polymerization
Reprogramming of Nucleic Acid Ligands: “Aptamers”
池袋 一典・セーボレー 那沙・阿部 公一
Kazunori IKEBUKURO, Nasa SAVORY, Koichi ABE
<要旨> アプタマーは、抗体に替わる新規分子認識素子として注目されている。その分子認識能は一次構造に依存するため、塩基配列の改良と最適化によって、目的に合った高い機能を示すアプタマーを獲得することができる。アプタマーの塩基配列の改良と最適化に関する最近の進歩と配列-機能相関の解析、今後の展望について述べる。
Keywords: Aptamers / Genetic Algorithms / In Silico Maturation / Sequence Optimization
トピックス COVER STORY: Topics and Products
Expansion of Genetic Code and Protein Function
芳坂 貴弘
Takahiro HOHSAKA
<要旨> We have developed a method for site-specific incorporation of non-natural amino acids into proteins through expansion of the genetic code. To encode non-natural amino acids, we have used a four-base codon CGGG which can be successfully decoded into non-natural amino acids by using chemically aminoacylated transfer RNA in a cell-free translation system. This method has been utilized to introduce various non-natural amino acids carrying photo-responsive, fluorescent, and polymer molecules. We have achieved the detection of ligand- or antigen-binding as fluorescence or FRET changes by introducing fluorescent non-natural amino acids into ligand-binding proteins and single-chain antibodies in a site-specific manner. The non-natural amino acid technique will be useful not only for artificial protein design but for polymer reprogramming.
Keywords: Protein / Genetic Code / Non-natural amino acid / Cell-free Translation / Fluorescence / FRET / Antibody
Bipedal Walking Template toward Sequence-Controlled Vinyl Polymers
大内 誠
Makoto OUCHI
<要旨> Toward syntheses of sequence-controlled vinyl polymers, a set of orthogonal dynamic covalent bonds, i.e., N-hydroxysuccinimide (NHS)-ester and 2-pyridil disulfide (SS-pyridine), were introduced as linkers between an initiator and a vinyl monomer for living radical polymerization. The sepcial linkers allowed iterative cycles consisting of single monomer addition, cleavage and functionalization, and reinstallation of vinyl groups under a bipedal walking template mechanism. The cycle was successfully repeated twice to demonstrate the adequacy of this protocol toward sequence regulation.
Keywords: Sequence / Vinyl Polymer / Living Radical Polymerization / Template / Orthogonal / Cyclization / Cleavage / Dynamic Covalent Bond
Design of Functional Peptides Using Informational Analysis
本多 裕之
Hiroyuki HONDA
<要旨> Peptides have attracted attention for their variety of biological functions. Computationally-assisted peptide screening and design have become invaluable tools in overcoming the inefficiency of peptide screening because there are too huge variants of peptides. Correlation between amino acid sequence and peptide function should be revealed by the computational approach. In this column, screening and design of both bile acid binding peptide and cell adhesion peptide will be introduced. The sequence rule was successfully acquired by computational analysis. Peptides designed according to the rule were found to express an active function.
Keywords: Peptide / Informatics / Amino Acid Sequence / Biological Function
Preparation of Polymer Aptamer from a Copolymer Library
星野 友
<要旨> Synthetic polymer aptamers are expected as robust and inexpensive substitute for biomacromolecular ligands. However, in contrast to biomacromolecular ligands, synthetic polymers, which are prepared through one-pot chain reaction, result in heterogeneous sequences and structures with a distribution of recognition sites. To obtain polymer aptamers with strong and specific binding affinity to target molecules, strategies to design and produce polymer aptamers with defined structure have to be developed. This article provides a brief review about recent efforts to develop the polymer aptamers consisting of combination of functional acrylamides.
Keywords: Aptamer / Acrylamide / Molecular Recognition / Multifunctional Polymer
Creation of Nucleic Acid Aptamers That Contain Unnatural Nucleotides
桒原 正靖
<要旨> Chemically modified nucleic acid aptamers have recently attracted attention due to the potential expandability of functions as therapeutic drugs, diagnostic agents, and biosensors. The author is engaged in enzymatic syntheses of modified nucleic acids and their applications to SELEX (Systematic Evolution of Ligands by EXponential enrichment) methods to create modified nucleic acid aptamers. To date, the author and coworkers have successfully obtained modified DNA aptamers specific for R-thalidomide derivative, l-glutamic acid, and a camptothecin derivative from base-modified DNA libraries. Furthermore, 2’,4’-BNA/LNA aptamers have first been acquired from DNA-based 2’,4’-BNA/LNA library using a capillary electrophoresis (CE)-SELEX method. Recent studies on nucleic acid aptamer development indicate positive effects on the introduction of functionalities in binding affinity and specificity. Further improvements of polymerase variants and selection methodologies will provide various modified nucleic acid aptamers for practical use.
Keywords: Aptamer / Polymerase Variant / Nucleoside Triphosphate / Capillary Electrophoresis / SELEX
グローイングポリマー Polymer Science and I: A Personal Account
Still Growing Up?
樫田 啓
<要旨> Nucleic acids are often recognized as homogeneous polymers and the creation of functional base-pairs is one of my passions. This personal account describes my reseach life on nucleic acids that is guided by warm-hearted supervisors and students.
高分子科学最近の進歩 Front-Line Polymer Science
Past, Present and Future of Single Polymer Chain Mechanics
中嶋 健・梁 暁斌
<要旨> Past, present and future of single polymer chain mechanics based on atomic force microscopy were reviewed, which is generally called as single molecule force spectroscopy (SMFS). Static SMFS can provide information such as persistent length and contour length appearing in a worm-like chain model. Thiol-terminated Poly(N-isopropylacrylamide) was used as an example study and its behavior change near its LCST was investigated. The temperature dependence of the plateau force at the low-extension region agreed well with the prediction by the pearl-necklace model developed by Prof. F. Tanaka. Two types of dynamic SMFS methods were also reviewed. The first noise-analysis SMFS may need future instrumental improvement. The second forced-oscillation SMFS measurements have resulted in a lot of interesting insights. As an example, the relaxation time of the polystyrene chain in N,N-dimethylformamide was measured and its dependence on the degree of polymerization was investigated. The Kirkwood model reproduced well the experimental results, while the necessity for a new concept of effective viscosity is proposed.
Keywords: Single Polymer Chain / Atomic Force Microscopy / Single Molecule Force Spectroscopy / Poly(N-isopropylacrylamide) / Relaxation Time / Kirkwood Model