Synthesis of Gramicidin S Analogs as β-Structured Functional Molecular Units

作为 β 结构功能分子单元的短杆菌肽 S 类似物的合成

基本信息

批准号：
10650847
负责人：
KAWAI Masao
金额：
$ 2.3万
依托单位：
Nagoya Institute of Technology
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
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

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.

制备了循环脱皮物抗生素（GS），具有分子内和分子间寡甲基桥的新型类似物，并研究了其抗菌活性。制作了有关其活性表现的新洞察力的结构 - 抗细菌活动。制备了picolinoylamylamiylamiylamiyllamy lamay酰胺群的衍生物，并研究了其二价金属离子结合特征。与Cu（II）和Zn（II）离子形成的二吡啶酰基衍生物形成稳定的1：1复合物，而在单质硅烷衍生物Cu（ii）离子介导的二聚体缔合的情况下，观察到了两个BIS（picollyl）amno组的GS的四丙基衍生物。表现出二核锌（II）复合物可促进HPNP（2-羟基丙基P-亚硝基苯基磷酸）的磷酸二酯键的切割，作为RNA模型底物。为了改善该功能性分子系统，含有D型苯胺的GS的类似物保留了D-苯基丙氨酸保留的保留，还保留了含有羟基普罗林的D-苯基丙氨酸的类似物，因为脯氨酸保留了脯氨酸保留的保留，因为其他官能团（例如诸如这些官能识别和/或活性控制）可以通过这些单一的抗脑料进行分析，以代替这些型氢化型组合，以代替这些水晶酸 - 抗脑料，以代替这些型氢化型抗氧化氢，以代替这些氢化型型氢化型氢化型 - 氧化和/或活性组。 GS的DI-BOC-TETRA-N-甲基衍生物已作为与GS相关化合物的成功晶体学分析的第二个例子，也是第一个提供令人满意准确的原子参数的示例。除了反平行的β-片类型主链链链氢键外，还观察到分子内侧链链链氢键相互作用。