Interaction between heteromolecules-Structural study and application of PNA-

异分子间的相互作用-PNA的结构研究及应用-

• 批准号: 07672427
• 负责人: DOI Mitsunobu
• 金额: $ 1.47万
• 依托单位: Osaka University of Pharmaceutical Sciences (OUPS)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672427/
• 关键词: PNA; PEPTIDE; STRUCTURE; INTERACTION; HETEROMOLECULE; NUCLEIC ACID; HETEROMDLECULE

Interactions between huge kinds of heteromolecules support the life of organs. The combination of simple interaction mode creates the complicated and functional structures. Therefore, the combination of interactions is very important for understanding function of bioactive compounds. Our investigation is focused on the interaction mode between nucleic bases and amino acids (protein).One characteristics in this project is using peptidic nucleic acid (PNA) which is combined with amino acids sequences. This peptide is a hybrid dipeptide having peptide backbone and nucleic bases in the peptide. Our structural investigation gave the following results.1 Basic unit of PNA(1) N-(2-aminoethyl) glycine was synthesized from 3-amino-1,2-propanediol quickly.(2) Substitution glycine for another amino acid make the distances between bases amino acid side chain shorter, and novel character was expected.(3) Combination of alpha-PNA brings freedom in selecting the position of PNA in peptide.2 Fluorescence titration of hybrid dipeptide(1) The dipeptide containing cytosine base and tryptophan shows relatively high affinity for all nucleic bases.3 X-ray crystal structure(1) Dipeptide containing Trp crystallized as highly hydrate state(2) Dipeptides containing Trp, Tyr, Ala, Phe and lle are associated in crystal(3) Association level is very high in the dipeptides containing Phe and lle.(4) Interaction between nucleic base and backbone (amino or carboxy group) are commonly observed in crystal structure.

巨大种类的杂大分子之间的相互作用支撑着器官的生命。简单互动模式的结合造就了复杂的功能结构。因此，相互作用的结合对于理解生物活性化合物的功能是非常重要的。我们的研究重点是核酸碱基与氨基酸(蛋白质)之间的相互作用模式。本项目的一个特点是使用了与氨基酸序列相结合的多肽核酸(PNA)。该多肽是一种具有多肽骨架和核酸碱基的杂合二肽。1.以3-氨基-1，2-丙二醇为原料，快速合成了PNA的基本单元N-(2-氨基乙基)甘氨酸。(2)用甘氨酸取代另一种氨基酸，缩短了碱基与氨基酸侧链之间的距离，具有新的性质。(3)α-PNA的结合使PNA在多肽中的位置选择更加自由。2.杂交二肽的荧光滴定(1)含有胞嘧啶碱基和色氨酸的二肽对所有的核酸碱都表现出较高的亲和力。3)含有Trp的二肽结晶为高水合物状态(2)含有Trp、Tyr、Trp的二肽ALA、Phe和LLE在晶体中缔合。(3)在含有Phe和LLE的二肽中缔合程度很高。(4)晶体结构中经常观察到核碱基与主链(氨基或羧基)的相互作用。

项目成果

M.Doi et al.: "Cytosine and Tryptophair hyhbrid dipeptide" Acta Crystallogr.Sect.C. (in press). (1998)

M.Doi 等人：“胞嘧啶和色氨酸杂合二肽”Acta Crystallogr.Sect.C。

M.Doi et al.: "Structure of N-Substituted Glycine(Peptcid)Monomer" Acta Crystallogr.Sect.C. (in press). (1998)

M.Doi 等人：“N-取代甘氨酸（肽）单体的结构”Acta Crystallogr.Sect.C。

M.Doi, et al.: "Cytosine and tnyptophan hybrid dipeptide." Acta Cnystallogr.Sect.C. (in press). (1998)

M.Doi 等人：“胞嘧啶和 tnyptophan 杂合二肽。”

Mitsunobu Doi, Mariko Tarui, Mihoko Ogata, Akiko Asano, Toshimasa Ishida: "Cytosine and trytophan hybrid dipeptide ; Structure of cytosinyl-L-tryptophan hexahydrates" Acta Crystallogr.Sect.C.(in press). (1998)

Mitsunobu Doi、Mariko Tarui、Mihoko Ogata、Akiko Asano、Toshimasa Ishida：“胞嘧啶和色氨酸杂合二肽；胞嘧啶基-L-色氨酸六水合物的结构”Acta Crystallogr.Sect.C.（印刷中）。

Mitsunobu Doi, Kazue Kinoshita, Akiko Asano, Ryuji Yoneda, Takushi Kurihara, Toshimasa Ishida: "Structure of N-Substituted Glycine (Peptoid) Monomer, N-tert-butyloxycarbonyl-N-benzylglycine" Acta Crystallogr.Sect.C.(in press). (1998)

Mitsunobu Doi、Kazue Kinoshita、Akiko Asano、Ryuji Yoneda、Takushi Kurihara、Toshimasa Ishida：“N-取代甘氨酸（类肽）单体，N-叔丁氧基羰基-N-苄基甘氨酸的结构”Acta Crystallogr.Sect.C.（出版中）