Studies on self-assembling peptides containing novel amino acids with hetero-rings in side-chains

侧链杂环新型氨基酸自组装肽的研究

• 批准号: 16550152
• 负责人: YAMADA Takashi
• 金额: $ 2.05万
• 依托单位: Konan University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16550152/
• 关键词: α, α-disubstituted glycine; α, α-di(2-pyridyl)glycine; α-phenyl-α-(2-pyridyl)glycine; amino acids with hetero-rings; separation of diastereomers; CD spectra; analysis of chirality; self-assembling peptides; Ugi反応; ピリジン環含有アミノ酸; ピラジン環含有アミノ酸; チアゾー

In this research project, we have intended to develop new self-assembling peptides containing novel α,α-disubstituted glycines with hetero-rings, and investigated synthesis, conformation and Cu-complex formation of various peptides containing novel α, α-disubstituted glycines with hetero-rings, α, α-di(2-pyridyl)glycine (2Dpy), α-phenyl-α-(2-pyridyl)glycine (2Ppg), α-methyl-α-(2-pyridyl)glycine (2Pmg), α-methyl-α-(2-pyrazyl)glycine (2Pzm) and α-methyl-α-(2-thiazolyl)glycine (2Tmg).1.Tripeptides (Z-AA_1-2Dpy/2Ppg-AA_3-OMe) containing 2Dpy and 2Ppg were synthesized by the Ugi reaction. NMR analysis revealed these peptides adopt a novel conformation in which each nitrogen atom of pyridine rings forms an intramolecular hydrogen bond with a hydrogen atom of an amide bond.2.The tripeptides containing 2Dpy were synthesized by the solid-phase Ugi reaction. By this method, yields of these peptides were markedly improved, compared with yields by the solution method.3.Tripeptides containing 2Pmg … More were first synthesized by the solid-phase Ugi reaction. These tripeptides adopt a unique conformation with an intramolecular hydrogen bond between 2Pmg-NH and the pyridine nitrogen.4.The 2Dpy-containing tripeptides afforded the 2:1 complex with Cu(II) ion, and the crystal structure was clarified by X-ray analysis. Further, ESR spectrum of the complex was also studied.5.A hexapeptide containing two 2Dpy residues was synthesized. The peptide adopts an extended conformation with four intramolecular hydrogen bonds between 2Dpy-NH and a pyridine nitrogen. Complex formation of the peptide with metal ions will be investigated.6.Chirality of 2Ppg in peptides was investigated by synthesis of tri-and tetrapeptides containing 2Ppg followed by separation of the diastereomers and X-ray crystal analysis, and measurement of CD spectra.7.Tripeptides, Z-AA_1-(N-Bzl)Xaa-AA_3-OMe (Xaa=2Pzm,2Tmg), containing other hetero-rings were synthesized by the Ugi reaction. In both peptides, the intramolecular hydrogen bonding between a pyrazine nitrogen and AA_3-NH and between a thiazole nitrogen and AA_3-NH, respectively, were observed. Stabilities of the intramolecular hydrogen bonding by a pyridine nitrogen, a thiazole nitrogen and a pyrazine nitrogen are compared. Less

本研究以新型α，α-双取代甘氨酸杂环自组装肽为研究对象，研究了新型α，α-双取代甘氨酸杂环自组装肽的合成、构象和铜配合物的形成（2-吡啶基）甘氨酸（2Dpy），α-苯基-α-（2-吡啶基）甘氨酸（2 Ppg），α-甲基-α-（2-吡啶基）甘氨酸（2 μ mg），α-甲基-α-（2-吡唑基）甘氨酸（2 Pzm）和α-甲基-α-（2-噻唑基）甘氨酸（2 Tmg）：1.通过Ugi反应合成了含有2Dpy和2 Ppg的三肽（Z-AA_1-2Dpy/2 Ppg-AA_3-OMe）。NMR分析表明，这些肽具有一种新的构象，即吡啶环上的每个氮原子与酰胺键上的一个氢原子形成分子内氢键。2.通过固相Ugi反应合成了含2Dpy的三肽。与溶液法相比，用此方法可显著提高这些肽的产率。3.含2Pmg ...更多信息 首先通过固相Ugi反应合成。2Dpy三肽与Cu（II）离子形成2：1的配合物，通过X射线衍射分析确定了配合物的晶体结构。5.合成了一个含两个2Dpy残基的六肽。该肽采用扩展构象，在2Dpy-NH和吡啶氮之间具有四个分子内氢键。6.合成了含2 Ppg的三肽和四肽，通过对非对映体的分离、X射线晶体分析和圆二色谱测定，研究了2 Ppg的手性。7.通过Ugi反应合成了含其他杂环的三肽Z-AA_1-（N-Bzl）Xaa-AA_3-OMe（Xaa= 2 Pzm，2 Tmg）。在这两种肽中，吡嗪氮和噻唑氮分别与AA_3-NH之间和AA_3-NH之间存在分子内氢键。通过吡啶氮，噻唑氮和吡嗪氮的分子内氢键的稳定性进行比较。少

项目成果

Synthesis and binding activities for opioid receptors of endomorphin and morphiceptin analogs containing conformationally constrained 1-aminocyclG alkane-1-carboxylicacids

含有构象限制的 1-氨基环G 烷-1-羧酸的内吗啡和吗啡肽类似物的阿片受体的合成和结合活性

• 期刊: Peptides 2006 (印刷中)
• 作者: S.Hirota;H.Okumura;S.Arie;K.Tanaka;M.Shionoya;T.Takebe;N.Funasaki;Y.Watanabe;山田隆己;山田隆己;T.Yamada;T.Yamada;T.Yamada;T.Yamada;T.Yamada;破入正行;山田隆己;村嶋貴之;破入正行;山田隆己;山田隆己;M.Hanyu;T.Yamada;T.Murashima;M.Hanyu;T.Yamada;T.Yamada;M.Hanyu;T.Yamada;T.Yamada;T.Yamada;M.Hanyu;M.Hanyu;T.Yamada;T.Yamada;山田隆己;破入正行;破入正行;T.Yamada;M.Hanyu;M.Hanyu;M.Hanyu;T.Yamada;T.Yamada
• 通讯作者: T.Yamada

Synthesis of tripeptides containing a very crowded a, a-disubstituted glycine with pyridine rings by solid-phase Ugi reaction

固相Ugi反应合成含有吡啶环非常拥挤的α,α-二取代甘氨酸的三肽

• 发表时间: 2004
• 期刊: Tetrahedron Lett. 45
• 作者: S.Hirota;H.Okumura;S.Arie;K.Tanaka;M.Shionoya;T.Takebe;N.Funasaki;Y.Watanabe;山田隆己;山田隆己;T.Yamada;T.Yamada;T.Yamada;T.Yamada;T.Yamada;破入正行;山田隆己;村嶋貴之;破入正行;山田隆己;山田隆己;M.Hanyu;T.Yamada;T.Murashima;M.Hanyu;T.Yamada;T.Yamada;M.Hanyu;T.Yamada;T.Yamada;T.Yamada;M.Hanyu;M.Hanyu;T.Yamada;T.Yamada;山田隆己;破入正行;破入正行;T.Yamada;M.Hanyu;M.Hanyu
• 通讯作者: M.Hanyu

A novel intramolecular hydrogen bonding between a side-chain pyridine ring and an amide hydrogen of the peptide backbone in trieptides containing the new amino acid, α,α-di(2-pyridyl)glycine

含有新氨基酸α,α-二(2-吡啶基)甘氨酸的三肽中侧链吡啶环和肽主链的酰胺氢之间的新型分子内氢键

• 发表时间: 2004
• 期刊: Org.Biomol.Chem. 2
• 作者: S.Hirota;H.Okumura;S.Arie;K.Tanaka;M.Shionoya;T.Takebe;N.Funasaki;Y.Watanabe;山田隆己;山田隆己;T.Yamada;T.Yamada;T.Yamada;T.Yamada;T.Yamada;破入正行;山田隆己;村嶋貴之;破入正行;山田隆己;山田隆己;M.Hanyu;T.Yamada;T.Murashima;M.Hanyu;T.Yamada;T.Yamada;M.Hanyu;T.Yamada;T.Yamada;T.Yamada;M.Hanyu;M.Hanyu;T.Yamada;T.Yamada;山田隆己;破入正行;破入正行;T.Yamada;M.Hanyu;M.Hanyu;M.Hanyu;T.Yamada
• 通讯作者: T.Yamada

Studies on intramolecular hydrogen bonding between the pyridine nitrogen and the amide hydrogen of the peptide: synthesis and conformational analysis of tripeptides containing novel amino acids with a pyridine ring

• DOI: 10.1002/psc.647
• 发表时间: 2005-07-01
• 期刊: JOURNAL OF PEPTIDE SCIENCE
• 影响因子: 2.1
• 作者: Hanyu, M;Ninomiya, D;Yamada, T
• 通讯作者: Yamada, T

Comparison of conformations of tetrapeptide diastereomers containing α-phenyl-α-(2-pyridyl)glycine

含α-苯基-α-(2-吡啶基)甘氨酸的四肽非对映异构体的构象比较

• 发表时间: 2006
• 期刊: Peptide Science 2006
• 作者: S.Hirota;H.Okumura;S.Arie;K.Tanaka;M.Shionoya;T.Takebe;N.Funasaki;Y.Watanabe;山田隆己;山田隆己
• 通讯作者: 山田隆己