Synthesis of Gramicidin S Analogs as β-Structured Functional Molecular Units
Synthesis of Gramicidin S Analogs as β-Structured Functional Molecular Units
批准号:
10650847
负责人:
KAWAI Masao
金额:
$2.3万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1998
资助国家:
日本
项目状态:
已结题
起止时间:
1998 至 2000
中文摘要
合成了具有分子内和分子间寡亚甲基桥的环状十肽抗生素短杆菌肽S(GS)类似物,并研究了它们的抗菌活性。结构与抗菌活性的关系为研究其抗菌活性提供了新的思路。合成了含吡啶甲酰胺基团的GS衍生物,并研究了它们与二价金属离子的结合特性。吡啶甲酰基衍生物与Cu(II)和Zn(II)离子形成稳定的1:1络合物,而吡啶甲酰基衍生物与Cu(II)离子形成稳定的2:1络合物.合成了含有两个吡啶甲酰基氨基的GS四吡啶甲酰基衍生物,并与Zn(II)离子形成稳定的1:2络合物.双核Zn(II)配合物被证明可以促进HPNP(2-羟丙基对硝基苯基磷酸)作为RNA模型底物的磷酸二酯键的裂解。为了改善这种功能性分子系统,含有D-酪氨酸残基代替D-苯丙氨酸残基的GS类似物以及含有羟脯氨酸残基代替脯氨酸残基的GS类似物,因为通过使用这些含有羟基的氨基酸残基可以引入额外的官能团,例如底物识别和/或活性控制。GS的甲基衍生物作为GS相关化合物的成功晶体学分析的第二个例子,也作为第一个例子,它提供了令人满意的准确的原子参数。除了反平行β折叠型主链-主链氢键外,还观察到分子内侧链-主链氢键相互作用。
英文摘要
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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K.Yamada 他3名およびM.Kawai: "Phosphodiester bond cleavage mediated by a cyclic β-sheet peptide-based dinuclear zinc(II) complex"J. Chem. Soc., Chemical Communications. 2000. 1315-1316 (2000)
K. Yamada 等人和 M. Kawai:“基于环状 β-片肽的双核锌 (II) 复合物介导的磷酸二酯键断裂”J. Chem.,化学通讯,2000 年。
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K.Yamada 他3名およびM.Kawai: "Convenient preparation of[Om(Tfa)2] and [Om(Boc)2,Om(Tfa)2']gramicidin S, versatile unsymmetricallv protected derivatives of gramicidin"J. Peptide Res.. 54. 168-173 (1999)
K. Yamada 等 3 人以及 M. Kawai:“[Om(Tfa)2] 和 [Om(Boc)2,Om(Tfa)2]短杆菌肽 S 的便捷制备,短杆菌肽的多功能非对称保护衍生物”J。决议.. 54. 168-173 (1999)
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K.Yamada 他8名およびM.Kawai: "Preparation and properties of novel gramicidin S analogs possessing a tri-, tetra-, or pentamethylene bridge between omithine side chains"J. Peptide Res.. 53. 611-617 (1999)
K. Yamada 等 8 人以及 M. Kawai:“在鸟氨酸侧链之间具有三、四或五亚甲基桥的新型短杆菌肽 S 类似物的制备和特性” J. Peptide Res.. 53. 611-617 (1999)
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K.Yamada 他3名およびM.Kawai: "Phosphodiester bond cleavage mediated by a cyclic β-sheet peptide-based dinuclear zinc (II) complex"Chemical Communications. 1315-1316 (2000)
K. Yamada 等人和 M. Kawai:“基于环状 β-片肽的双核锌 (II) 复合物介导的磷酸二酯键裂解”,化学通讯 1315-1316。
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R.Akasaka 他7名およびM.Kawai: "Preparation and properties of bridged gramicidin S analogs possessing various intra-or intermolecular linkers between basic side chains"Peptide Science 2000. (印刷中). (2001)
R.Akasaka 等 7 人以及 M.Kawai:“在基本侧链之间具有各种分子内或分子间连接基的桥接短杆菌肽 S 类似物的制备和特性”Peptide Science 2000。(出版中)。
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