有機合成化学協会誌
Online ISSN : 1883-6526
Print ISSN : 0037-9980
ISSN-L : 0037-9980
生体高分子の有機化学：合成が拓く機能解明と制御へのアプローチ
  • 公開日: 2026/03/06      更新日: 2026/03/06

    生命現象の根幹を担う核酸、タンパク質、複合糖質などの生体高分子。有機合成化学は、これら天然の精密な構造を構築するだけでなく、その機能を模倣・拡張した人工分子を創製することで、生命科学研究に新たな視座を与え続けています。
    本スポットライトでは、1982年から約30年にわたる総合論文から、生体高分子を題材とした有機合成化学の多岐にわたる挑戦を集約しました。分子レベルでの精密な設計と合成が、いかにして生命機能の解明や制御への道を切り拓いてきたか、基礎となる合成研究から生化学への展開を含め、その発展の軌跡をご覧ください。
    （編者一同）

23件中1～20件の論文を表示しています
  • 40 巻 (1982) 8 号 p. 735-743      公開日: 2026/03/06
    DNAの部位特異的な化学反応と分子認識
    斎藤 烈, 杉山 弘
    The molecular recognition of DNA by small molecules including bisintercalators has been described. Site-specific chemical reactions of DNA are next reviewed. These include i) reactions of DNA with oxygen-dependent antibiotics such as bleomycin, neocarzinostatin and camptothecin, and ii) single strand cleavage induced by artificial compound-metal-O2 systems. Sequence specific photoreaction between DNA and psoralenes is briefly discussed. A new method for selective removal of thymine from DNA utilizing photochemical reaction is also described in detail.
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  • 42 巻 (1984) 6 号 p. 507-513      公開日: 2026/03/06
    細菌表層生理活性物質リピドAの構造と合成
    芝 哲夫, 楠本 正一
    Bacterial surface substance has been known to possess the endotoxic activity which is located at the lipid A part. Although a chemical structure for lipid A was early proposed, exact positions of fatty acids linked to the disaccharide skeleton have been ambiguous. We succeeded to obtain a chemically pure sample of natural E. coli mutant lipid A. From results obtained by 2 D-NMR analysis of this sample, we proposed a revised structure for lipid A. 2, 2'-N, 3, 3'-O-Tetraquis [(R) -3-hydroxytetradecanoyl] -β (1-6) -D-glucosamine disaccharide 1, 4'- diphosphate synthesized according to the proposed structure was quite identical with the natural acidic precursor of lipid A. This is the first achievement to establish the correct chemical structure of the natural lipid A by organic synthesis.
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  • 43 巻 (1985) 10 号 p. 908-920      公開日: 2026/03/06
    DNAの認識と切断
    橋本 祐一, 首藤 紘一
    Bis-intercalators and hemin-intercalators (Hemin-Glu-P-1's) which recognize and/or cleave DNA were designed and synthesized. 2-Aminodipyrido [1, 2-a : 3', 2' -d] imidazoles (Glu-P's) which are potent muta-carcinogens isolated from a pyrolysate of L-glutamic acid were used as intercalator moieties. Bis-intercalators possess extremely high affinity toward double stranded DNA and stabilize the double helix structure of DNA from heat denaturation effectively. Hemin-Glu-P-1's cleaved DNA at G-C and G-T sequences preferentially. Glu-P-1 moiety which recognizes DNA by intercalation and a functional group which can be an intramolecular fifth ligand of the ferrous ion in the hemin moiety are required for strong DNA-cleaving ability. The mode of DNA-cleaving reaction of Hemin-Glu-P-1's is quite similar to that of bleomycin (BLM). In other words, Hemin-Glu-P-1's are functional analogs of BLM. The mechanism of DNA cleavage by Hemin-Glu-P-1's and by BLM is not single. One of the mechanisms involves two bases elimination from the DNA.
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  • 43 巻 (1985) 11 号 p. 1061-1072      公開日: 2026/03/06
    核酸の機能・構造研究と化学修飾
    上田 亨
    The use of modified base or alteration of base sequences, and chemical modifications are reviewed for the study of nucleic acid functions and structures. The examples included are the point mutation of promoter region of rDNA gene, replacement of the certain bases with modified ones in the recognition sequence of restriction endonuclease Bgl II and Sau 3AI, ozone-degradation of supercoiled plasmid DNA, replacement of nucleotides in the anticodon region of formylmethionine tRNA, and chemical modification of mouse 5S ribosomal RNA.
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  • 44 巻 (1986) 11 号 p. 1022-1028      公開日: 2026/03/06
    核酸光化学の新展開
    斉藤 烈
    The author's results on the organic photochemistry of nucleic acid derivatives have been reviewed. These include, i) a novel photoreaction between thymidine and primary amines, ii) its use in determining T residues of DNA fragments in DNA sequencing, iii) new photochemical methods for C-C bond formation at C- 5 and C- 6 positions of pyrimidine nucleosides, and iv) a selective deoxygenation method of ribonucleosides to 2'- deoxy-and 2', 3'-dideoxyribonucleosides by utilizing photosensitized electoron-transfer reaction.
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  • 49 巻 (1991) 8 号 p. 762-769      公開日: 2026/03/06
    核酸を選択的に切断する人工材料の開発を目指して
    小宮山 真
    Highly active catalysts for the hydrolysis of phosphodiester linkage in RNAs and DNAs, which are applicable to artificial ribonucleases and nucleases, have been reported. Oligoamines such as ethylenediamine and triethylenetetramine (trien), as well as cobalt (III) complexes such as [Co (trien) (H2O) 2] 3+ and [Co (tme) 2 (H2O) 2] 3+ (tme : 1, 1, 2, 2-tetramethylethylenediamine), are so active (105 to 106 fold acceleration) that RNAs are promptly hydrolyzed near neutrality. The large activities are ascribed to intramolecular acid-base cooperation in the catalysts. In addition, pheophorbide, a derivative of chlorophyll, efficiently cleaves DNAs under irradiation of visible light, even in the absence of oxygen. The photocleavage proceeds via a novel mechanism, which involves direct attack of the dye to DNAs (and not attack by singlet oxygen). Simple structures of these catalysts as well as their large activities strongly indicate high potentialities as the catalytic sites in artificial ribonucleases and nucleases.
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  • 55 巻 (1997) 5 号 p. 384-392      公開日: 2026/03/06
    DNA塩基配列およびDNA湾曲の認識-人工リプレッサーの設計に向けて
    杉浦 幸雄, 永岡 真
    DNA recognition is a very important phenomenon in biology and chemistry, and the molecular basis of the sequence-specific DNA binding is the subject of investigations aimed at the rational design of molecules with specific biological activities. Minor-groove-binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids achieve affinities and specificities comparable to DNA binding proteins. The synthetic oligosaccharide moiety of the antibiotic calicheamicin and the head-to -head dimer of this oligosaccharide bind to the minor groove of DNA in a sequence-selective manner preferring distinct target sequences. Zinc-finger libraries with different DNA-binding specificities based on a one-finger-three-nucleotide code have been developed successfully. On the other hand, DNA bending is also important regulators of biological process. Sequence-specific DNA bending ligands are designed to bind two noncontiguous sites in the major groove and induce a bent in the DNA. Molecules that specifically bind and bent any predetermined DNA sequence in the human genome would be useful tools in molecular biology and potentially in human medicine.
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  • 56 巻 (1998) 2 号 p. 125-133      公開日: 2026/03/06
    合成ペプチドによるイオンチャネル機能の創出
    二木 史朗
    To create artificial ion channels using synthetic peptides is one of the challenges of the de novo design of artificial proteins not only to obtain highly functional artificial molecules but also to understand the basic mechanisms of natural ion channel proteins. Amphiphilic helical peptides of 20 amino acid residues were reported to assemble with each other in lipid bilayers to form ion channels. To obtain more organized channels, efforts have been directed toward controlling the assembly by template molecules. Not only α-helical peptides, but also peptide nanotubes and gramicidin-like molecules were developed as channel molecules where the assembly was stabilized by hydrogen bonding between the molecules. We have developed three approaches to construct artificial helical proteins comprising helices with individual amino acid sequences. Using one of these approaches, four helices corresponding to the voltage sensor (S 4 in repeat I-IV) of the sodium channel were tethered on a peptide template to afford a protein having ion channel activity with rectification.
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  • 57 巻 (1999) 3 号 p. 194-205      公開日: 2026/03/06
    3本鎖形成オリゴヌクレオチドを利用した遺伝子制御とDNAベンド
    秋山 泰身
    Thermodynamic property of triple helix and the mechanism of inhibition of mRNA transcription by triple helix formation are summarized in this review. I also mention on the artificial DNA bending system in which the antiparallel triple helix motif and synthetic linker consisting of polyether nucleotide units are utilized as the bender. Systematic analysis of this system revealed the anisotropic flexibility of DNA. Thus, DNA seems to be more flexible in minor groove direction as compared to that expected from the classic elastic coil and elastic rod model of duplex DNA.
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  • 58 巻 (2000) 1 号 p. 2-13      公開日: 2026/03/06
    コンホメーション固定による人工機能核酸の合成
    関根 光雄
    Recent studies of the synthesis of oligonucleotides incorporating conformationally locked nucleoside or nucleotide building blocks have been comprehensively reviewed in connection with the antisense stratagy as well as creaction of new functions of DNA/RNA. The synthesis, and conformational properties of a wide varaiety of nucleoside derivatives locked by introduction of three, four, and five membered-ring systems to the deoxyribose or ribose moiety have been described. The hybridization abilities of oligonucleotides incorporating these locked-nuucleosides are also discussed. In addition, this review deals with the synthesis and properties of conformationally fixed cyclouridylate derivatives bridged between the uracil and the 5'-phosphate of 5'-uridylic acids and their successful application to the construction of bent DNA and RNA.
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  • 62 巻 (2004) 10 号 p. 1026-1037      公開日: 2026/03/06
    3本鎖DNA認識コード拡張のための人工ヌクレオシドの開発
    谷口 陽祐, 佐々木 茂貴
    Triplex-forming oligonucleotides (TFOs) are potential DNA-targeting molecules, and would become powerful tools for genomic research. However, the problem that the stable triplexes form only with homopurine : homopyrimidine sequences has not been generally solved in spite of extensive studies. In this study we have developed new base analogs (WNA) constructed of three parts, a benzene ring, a heterocyclic ring, and a bicyclic skeleton to hold these two parts. Among a number of WNA analogs, we have determined two useful WNA analogs, WNA-/βT and WNA-/βC, for selective stabilization of triplexes at a TA and a CG interrupting site with higher stability than the natural-type triplexes, respectively. The results of this study will provide useful information for the design of new WNA analogs to overcome inherent problems for further expansion of triplex recognition codes.
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  • 63 巻 (2005) 1 号 p. 63-75      公開日: 2026/03/06
    ペプチド核酸の新展開
    和田 健彦, 井上 佳久
    Peptide nucleic acid (PNA), which has been proposed by Peter E. Nielsen in 1991, is one of the most typical and successful synthetic nucleic acid model compound, called an artificial nucleic acid, with extremely attractive and excellent properties, such as exactly sequence selective binding not only to complementary DNA but also to RNA, highly chemical and biological stability, forming very tight and stable complex with complementary DNA and RNA, and so on. Still, PNA also shows same inherent and crucial drawbacks, such as low solubility against aqueous solution, low cell membrane permeability, and uncertain direction of DNA/RNA sequence recognition. Thus, in order to improve these properties, a number of PNA derivatives have been proposed. In this review paper, we would like to give an overview of these strategies and properties of PNA derivatives and present our proposed novel strategy for active external reversible control of DNA/RNA recognition with peptide ribonucleic acid, PRNA.
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  • 63 巻 (2005) 4 号 p. 325-338      公開日: 2026/03/06
    糖-インターカレーター複合型人工DNA光切断分子の分子デザインと機能発現制御
    戸嶋 一敦
    Studies of the interaction between the small molecules and DNA, especially the effects of the structural characteristics of the small molecules on the DNA interaction, are very important for the design of DNA targeting new drugs. In this context, the development of photochemical DNA cleaving agents, which selectively cleave DNA by irradiation with light of a specific wavelength under mild conditions and without any additives such as metals and reducing agents, is very interesting from chemical and biological standpoints and offers considerable potential in medicine especially in the post-genome era. In this article, the molecular design, chemical synthesis, DNA photocleaving property and photo-selective cytotoxicity of such novel and artificial light activatable DNA cleaving agents, which consist of DNA intercalator and carbohydrate, are described
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  • 63 巻 (2005) 10 号 p. 1016-1027      公開日: 2026/03/06
    DNAの機能と構造を操るケミカルバイオロジー
    板東 俊和, 杉山 弘
    Fifty years after the discovery of the double helical structure of DNA, the complete sequence of the human genome has been determined. All genetic information, which is necessary for life, is written in 30 billion base pairs of DNA. Many diseases, including cancer, hereditary and viral diseases, can be understood at the DNA sequence level. Local DNA conformations are thought to play an important role in biological processes such as gene expression. Therefore, DNA sequences and local DNA conformation are targets of novel drugs that would precisely switch certain genes on or off. Modified bases that perform various functions can also be incorporated into defined DNA sequences. Since DNA can be amplified by PCR and in other organisms, DNA becomes a promising unit for nanotechnology applications. In this review, we focus on the sequence and conformation-specific chemical reactions that occur in DNA, and the prospective uses of the chemical biology of DNA will be discussed.
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  • 64 巻 (2006) 5 号 p. 492-501      公開日: 2026/03/06
    有機合成化学による糖タンパク質糖鎖の機能解明
    戸谷 希一郎, 萩原 伸也, 伊藤 幸成
    High-mannose-type oligosaccharides, which are co-translationally introduced to nascent polypeptides, play important roles in protein quality control. This process is very complex, involving a number of lectins, chaperones and glycan processing enzymes. For example, calnexin (CNX) and calreticulin (CRT) are molecular chaperons that recognize mono-glucosylated form of high-mannose-type glycans. UDP-Glucose : glycoprotein glucosyltransferase (UGGT) only glucosylates high-mannose-type glycans of unfolded glycoproteins. Fbs 1 is a part of ubiquitin ligase that recognizes sugar chains. Although recent studies have clarified properties of these proteins, most of them used oligosaccharides derived from natural source, which contain structural heterogeneity. In order to gain a precise insight about protein quality control, we comprehensively synthesized high-mannose-type glycans associated with protein quality control system. Additionally, during our investigations of artificial glycoproteins having homogeneous oligosaccharides, a novel non-peptidic substrate for UGGT was discovered. Using these synthetic oligosaccharide probes, we quantitatively evaluated the activity of CRT, Fbs 1 and UGGT.
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  • 64 巻 (2006) 11 号 p. 1122-1131      公開日: 2026/03/06
    Molecular Design of Polyamines and Related Compounds for Controlled DNA Folding Transition
    Anatoly A. Zinchenko, Ning Chen, Shizuaki Murata
    A library of designed DNA compaction agents based on multicationic polyamines, which can fold a DNA polymer chain into condensates with high density due to negative charge neutralization of DNA, are synthesized, and the structure-activity relationship in DNA compaction is investigated. It becomes obvious that the activity is strongly affected by non-electrostatic interactions with DNA, such as hydrophobic (hydrophilic), intercalation, and chirality effects, as well as by efficiency of charge interactions and geometry matching between charged groups of DNA and compaction agents.
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  • 65 巻 (2007) 7 号 p. 709-714      公開日: 2026/03/06
    光応答性人工核酸を用いた遺伝子操作および遺伝子解析
    藤本 健造
    DNA engineering, the basis of modern protein engineering, has been developed since the 1960s with many discoveries, including those of various restriction enzymes and polymerases, and a number of Nobel laureates for their contributions to, for example, the PCR method or DNA sequencing method. The existing biotechnology is thus essential to basic researches in the present DNA analysis or biochemistry. While many methods for enzymatic and chemical ligation of DNA fragment via a native phosphodiester bond or non-native linkages have been demonstrated, there are only a few methods for photoinduced non-enzymatic chemical ligation. The merit of the photochemical ligation avoiding the need for additional reagent is obvious. Furthermore, their actions are controllable within space and time by the choice of proper irradiation methods. The photoligation methods can be used as a tool for DNA engineering and nanotechnology, and as photoregulated diagnostic and therapeutic agents. Thcrcforc, the targct in my research is the development about phototriggered DNA manipulation via intelligent nucleic acids toward for the next generation DNA manipulation.
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  • 67 巻 (2009) 7 号 p. 680-687      公開日: 2026/03/06
    オスミウム-DNA錯体の作成と利用
    岡本 晃充
    Nucleic acids often acquire new functions by forming a variety of complexes with metal ions. Osmium, in an oxidized state, also reacts with C5-methylated pyrimidines in the presence of bipyridine to give a stable ternary complex. We have designed a bipyridine-attached adenine derivative for sequence-specific osmium complexation. Sequence-specific osmium complexation was achieved by hybridization of a short DNA molecule containing this functional nucleotide to a target DNA sequence, and resulted in the formation of a crosslinked structure. The interstrand crosslink clearly distinguished methylated cytosines from unmethylated cytosines, and was used to quantify the degree of methylation at a specific cytosine in the genome.
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  • 68 巻 (2010) 3 号 p. 217-227      公開日: 2026/03/06
    擬天然物特殊ペプチドのプログラム翻訳合成と応用
    樋口 岳, 菅 裕明
    The translation machinery is generally designated to synthesize polypeptides consisting of 20 proteinogenic (natural) amino acids. Significantly, the ribosomal synthesis is employed in mRNA–template dependent manner, i.e. the sequence of mRNA dictates that of polypeptide according to the genetic code, enabling us to design the peptide sequence by simply preparing the corresponding mRNA or its DNA as the template for transcription. From the synthetic point of view, however, the fact that the useable monomers are limited to 20 proteinogenic amino acids is a serious restriction for the preparation of peptide library with high chemical diversities. In this review, we shall discuss an emerging new technology, referred to as genetic code reprogramming, that allows us to express natural product–like non–standard peptides using a reconstituted cell–free translation system. This technology will open a new avenue for the discovery of a new class of non–standard peptides.
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  • 68 巻 (2010) 9 号 p. 911-919      公開日: 2026/03/06
    ペプチドチオエステル合成法の最近の進展
    重永 章, 佐藤 浩平, 大高 章
    Investigations of biological processes by using peptide, protein, or its derivative are undoubtedly valuable. In this field, chemical synthesis of native or modified peptides/proteins is indispensable. Fragment condensation strategy, such as thioester method or native chemical ligation, is widely used for chemical synthesis of large peptides and proteins. C-Terminal peptide/protein thioesters have been used as building blocks for the fragment condensation strategy. Therefore, development of methodologies for preparing C-terminal peptide/protein thioesters is one of the most attracting theme in recent peptide/protein chemistry field. In this review, the methodologies for preparing C-terminal peptide/protein thioesters utilizing chemistry, biochemistry, or gene engineering are summarized.
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