| Project/Area Number |
10650847
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Synthetic chemistry
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| Research Institution | Nagoya Institute of Technology |
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Principal Investigator |
KAWAI Masao Nagoya Institute of Technology,Faculty of Engineering, Professor, 工学部, 教授 (60161270)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKI Shuki Nagoya Institute of Technology,Faculty of Engineering, Professor, 工学部, 教授 (30115670)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1999: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | gramicidin S / methylene-bridged analogs / dimeric cyclic peptides / antibacterial activity / dinuclear Zn(II) complex / phosphodiester bond cleavage / hydroxyproline-containing analog / X-ray crystallographic analysis / 溶血活性 / β-シート型会合配座 / モノ修飾グラミシジンS / ピコリノイル誘導体 / 銅イオン錯体 / β-シート型分子間会合 / 分子内架橋誘導体 / 分子間架橋二量体 |
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| Research Abstract |
Novel analogs of the cyclic decapeptide antibiotic, gramicidin S (GS), possessing intra- and intermolecular oligomethylene bridge were prepared and their antibacterial activity was studied. The structure-antibacterial activity relationships afforded new insight concerning the manifestation of their activity.
Picolinoylamide group-containing derivatives of GS were prepared and their divalent metal ion-binding characteristics were investigated. The dipicolinoyl derivative formed stable 1:1 complex with Cu(II) and Zn(II) ions, while in the case of monopicolinoyl derivative Cu(II) ion-mediated dimeric association was observed.
The tetrapicolyl derivative of GS containing two bis(picolyl)amino groups were prepared and were shown to form a stable 1:2 complex with Zn(II) ion. The dinuclear Zn(II) complex was shown to promote the cleavage of the phosphodiester bond of HPNP (2-hydroxypropyl p-nitrophenyl phosphate) as an RNA model substrate. For the purpose of improving this functional molecular system the analogs of GS containing D-tyrosine residues in place of D-phenylalanine residues and also those containing hydroxyproline residues in place of proline residues since additional functional groups such as substrate-recognition and/or activity controle could be introduced by the use of these hydroxy group-containing amino acid residues.
X-ray single crystal analysis of a di-Boc-tetra-N-methyl derivative of GS has been performed as the second example of successful crystallographic analysis of GS-related compounds and also as the first example which afforded satisfactorily accurate atomic parameters. Intramolecular side chain-main chain hydrogen-bonding interactions were observed in addition to the antiparallel β-sheet type main chain-main chain hydrogen bonds.
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