研究者詳細 - 阿部　洋

Intermolecular transfer of aminoacylated adenosine towards chemical aminoacylation of tRNA. 査読有り

Liu M, Jinmei H, Fukuzono K, Abe H, Ito Y

Nucleic acids symposium series (2004) ( 51 ) 頁： 365 - 6 2007年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nucleic acids symposium series (2004)

We synthesized two oligonucleotides: one is DNA conjugated with adenosine derivative at 5' terminus as a donor, another RNA phosphorothioated at 3' terminus as an acceptor. By hybridization of the two oligonuleotides, the adenosine derivative was transferred from the donor DNA to the acceptor RNA. In this study, O, O'-isopropylidene-protected adenosine derivative and aminoacylated adenosine were successfully transferred from the donor to acceptor RNA. By use of tRNA instead of the acceptor RNA, the chemical aminoacylation of tRNA by unnatural amino acid is expected.

DOI： 10.1093/nass/nrm183

Scopus

Synthesis of adenophostin A analogues conjugating an aromatic group at the 5 '-position as potent IP3 receptor ligands 査読有り

Tetsuya Mochizuki, Yoshihiko Kondo, Hiroshi Abe, Stephen C. Tovey, Skarlatos G. Dedos, Colin W. Taylor, Michael Paul, Barry V. L. Potter, Akira Matsuda, Satoshi Shuto

JOURNAL OF MEDICINAL CHEMISTRY 49 巻 ( 19 ) 頁： 5750 - 5758 2006年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER CHEMICAL SOC

Previous structure-activity relationship studies of adenophostin A, a potent IP3 receptor agonist, led us to design the novel adenophostin A analogues 5a-c, conjugating an aromatic group at the 5'-position to develop useful IP3 receptor ligands. The common key intermediate, a D-ribosyl alpha-D-glucoside 10 alpha, was stereoselectively synthesized by a glycosidation with the 1-sulfinylglucoside donor 11, which was conformationally restricted by a 3,4-O-cyclic diketal protecting group. After introduction of an aromatic group at the 5-position of the ribose moiety, an adenine base was stereoselectively introduced at the anomeric beta-position to form 7a-c, where the tetra-O-i-butyryl donors 9a-c were significantly more effective than the corresponding O-acetyl donor. Thus, the target compounds 5a-c were synthesized via phosphorylation of the 2', 3", and 4"-hydroxyls. The potencies of compounds 5a-c for Ca2+ release were shown to be indistinguishable from that of adenophostin A, indicating that bulky substitutions at the 5'-position of adenophostin A are well-tolerated in the receptor binding. This biological activity of 5a-c can be rationalized by molecular modeling using the ligand binding domain of the IP3 receptor.

DOI： 10.1021/jm060310d

Design and synthesis of 5'-deoxy-5'-phenyladenophostin A, a highly potent IP3 receptor ligand. 査読有り

Mochizuki T, Kondo Y, Abe H, Taylor CW, Potter BV, Matsuda A, Shuto S

Organic letters 8 巻 ( 7 ) 頁： 1455-8 2006年3月

Design and synthesis of 5 '-deoxy-5 '-phenyladenophostin A, a highly potent IP3 receptor ligand 査読有り

T Mochizuki, Y Kondo, H Abe, CW Taylor, BVL Potter, A Matsuda, S Shuto

ORGANIC LETTERS 8 巻 ( 7 ) 頁： 1455 - 1458 2006年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER CHEMICAL SOC

5'-Deoxy-5'-phenyladenophostin A (5), designed as a useful IP3 receptor ligand based on the previous structure-activity relationship studies, was successfully synthesized via two key stereoselective glycosidation steps. This compound proved to be a highly potent IP3 receptor agonist.

DOI： 10.1021/o10602710

A systematic study of C-glucoside trisphosphates as myo-inositol trisphosphate receptor ligands. Synthesis of beta-C-glucoside trisphosphates based on the conformational restriction strategy 査読有り

M Terauchi, H Abe, SC Tovey, SG Dedos, CW Taylor, M Paul, M Trusselle, BVL Potter, A Matsuda, S Shuto

JOURNAL OF MEDICINAL CHEMISTRY 49 巻 ( 6 ) 頁： 1900 - 1909 2006年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER CHEMICAL SOC

beta-C-Glucoside trisphosphates having a C2 side chain (3,7-anhydro-2-deoxy-D-glycero-D-gulo-octitol 1,5,6-trisphosphate, 11) and a C3 side chain (4,8-anhydro-2,3-dideoxy-D-glycero-D-gulo-nonanitol 1,6,7-trisphosphate, 12) were designed as structurally simplified analogues of a potent D-myo-inositol 1,4,5-trisphosphate (IP3) receptor ligand, adenophostin A. Construction of the beta-C-glucosidic structure, which was the key to their synthesis, was achieved by two different methods based on the conformational restriction strategy: (1) radical cyclization with a temporary connecting silicon tether and (2) silane reduction of glyconolactols having an anomeric allyl substituent. Using these methods, the target beta-C-glycoside trisphosphates 11 and 12 were successfully synthesized. A structure-activity relationship was established on a series of C-glucoside trisphosphates, including the previously synthesized related compounds, which were a C-glycosidic analogue 3 of adenophostin A, its uracil congener 5, alpha-C-glucoside trisphosphates 7-9 having a C1, C2, or C3 side chain, and the beta-C-glucoside trisphosphates 10-12 having a C1, C2, or C3 side chain. The O-glycosidic linkage of adenophostin A and its analogues proved to be replaced by the chemically and biologically more stable C-glycosidic linkage. The alpha-C2-glucoside trisphosphate 8 stimulates Call release with a potency similar to that of IP3 in spite of its simplified structure, indicating a better fit to the receptor than the beta-C-glucoside trisphosphates and also the alpha-congeners having a shorter or longer C1 side chain, which was supported by molecular modeling using the ligand binding domain of the IP3 receptor.

DOI： 10.1021/jm051039n

Flow cytometric detection of specific RNAs in native human cells with quenched autoligating FRET probes. 査読有り

Abe H, Kool ET

Proceedings of the National Academy of Sciences of the United States of America 103 巻 ( 2 ) 頁： 263-8 2006年1月

Structure analysis of oligonucleotide in organic solvent 査読有り

Hiroshi Abe, Naoko Abe, Yoshihiro Ito

Nucleic Acids Symposium Series 50 巻頁： 25 - 26 2006年

Structure analysis of oligonucleotide in organic solvent. 査読有り

Abe H, Abe N, Ito Y

Nucleic acids symposium series (2004) ( 50 ) 頁： 25 - 6 2006年

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nucleic acids symposium series (2004)

Oligonucleotide has been used as functional molecule such as recording device, or catalyst for chemical reaction. However, that utility has been limited, because it is only soluble in water. Recently, we succeeded in making chemically modified DNA which is clearly soluble in organic solvent. Using this technique, G-quadruplex was constructed in non-polar organic solvent such as 1,2-dichloroethane. The structure was analyzed by CD spectra.

DOI： 10.1093/nass/nrl013

Scopus

新機能性核酸・タンパク質を生み出すコンビナトリアル・バイオエンジニアリング

阿部洋、和田章、伊藤嘉浩

生物工学会誌 84 巻 ( 8 ) 頁： 309 2006年

Synthesis of 4,8-anhydro-D-glycero-D-ido-nonanitol 1,6,7-trisphosphate as a novel IP3 receptor ligand using a stereoselective radical cyclization reaction based on a conformational restriction strategy 査読有り

M Terauchi, Y Yahiro, H Abe, S Ichikawa, SC Tovey, SG Dedos, CW Taylor, BVL Potter, A Matsuda, S Shuto

TETRAHEDRON 61 巻 ( 15 ) 頁： 3697 - 3707 2005年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

4,8-Anhydro-D-glycero-D-ido-nonanitol 1,6,7-trisphosphate (9), designed as a novel IP3 receptor ligand having an alpha-C-glycosidic\ structure, was synthesized via a radical cyclization reaction with a temporary connecting allylsilyl group as the key-step. Phenyl 2-O-allyldimethylsilyt-3,4-bis-O-TBS-1-seleno- beta-D-glucopyranoside (10a), conformationally restricted in the unusual C-1(4)-conformation, was treated with Bu3SnH/AIBN to form the desired alpha-cyclization product 16a almost quantitatively. On the other hand, when a conformationally unrestricted O-benzyl-protected 2-O-allyldimethylsilyl -l-selenoglucoside 15 was used as the substrate, the radical reaction was not stereoselective and gave a mixture of the alpha-and beta-products. From 16a, the target C-glucoside trisphosphate 9 was synthesized via phosphorylation of the hydroxyls by the phosphoramidite method. During the synthetic study, an efficient procedure for the oxidative C-Si bond cleavage, via a nucleophilic substitution at the silicon with p-MeOPhLi followed by Fleming oxidation, was developed. The C-glycoside 9 was found to be a full agonist for Ca2+ mobilization, although its activity was weaker than that of the natural ligand IP3. Thus, the alpha-C-glucosidic structure was shown to be a useful mimic of the myo-inositol backbone of IP3. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2005.02.025