Non-proteinogenic amino acids - asymmetric synthesis, secondary structure, and biological activity -

非蛋白氨基酸——不对称合成、二级结构和生物活性——

• 批准号: 13672219
• 负责人: TANAKA Masakazu
• 金额: $ 2.24万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672219/
• 关键词: α,α-disubstituted amino acids; helix; conformation; peptide; diethylglycine; Aib; X-ray crystallography; X線構造解析; 光学活性環状アミノ酸; X-線結晶解析; α-エチル化アミノ酸; アルキル化アミノ酸

Optically active α,α-disubstituted amino acids were synthesized using (S,S)-cyclohexane-1,2-diol as a chiral auxiliary. Homo- and hetero-peptides containing α-ethylated α,α-disubstituted amino acid, αEtLeu in Aib and Deg sequences were prepared, and also heteropeptide constituted of diverse α-ethylated α,α-disubstituted amino acids was synthesized. The conformation of pentapeptides was studied by using CD, FT-IR, H NMR, and X-ray. In solution, the dominant conformation of heteropeptide Tfa-[(S)-αEtVal-(S)-αEtLeu-(S)-αEtNva-Deg-(S)-αEtNle]-OEt was a fully planar C_5-conformation, and those of the other peptides were 3_<10>-helical structures. In the crystalline state, all pentapeptides showed the 3_<10>-helical structures. Furthermore, we synthesized chiral cyclic α,α-disubstituted amino acids starting from dimethyl tartrate, and prepared its homo- and heteropeptides. The conformation of its peptides seem to be formed the 3_<10>-helical structure preferentially. The antibacterial activity of peptides was examined, but none of peptides showed strong activity.

以（S，S）-环己烷-1，2-二醇为手性助剂合成了光学活性的α，α-二取代氨基酸。制备了Aib和Deg序列中含有α-乙基化α，α-二取代氨基酸、α-EtLeu的同源肽和异源肽，以及由不同α-乙基化α，α-二取代氨基酸组成的异源肽。用圆二色谱、红外光谱、核磁共振氢谱和X射线衍射等方法研究了五肽的构象。在溶液中，杂肽Tfa-[（S）-αEtVal-（S）-αEtLeu-（S）-αEtNva-Deg-（S）-αEtNle]-OEt的主要构象为全平面C5-构象，其余杂肽的主要构象为3_<10>-螺旋结构。在结晶状态下，所有五肽均为3<10>_螺旋结构。以酒石酸二甲酯为起始原料，合成了手性环状α，α-二取代氨基酸，并制备了其同肽和杂肽。其多肽的构象似乎优先形成3_<10>-螺旋结构。检测了肽的抗菌活性，但没有肽显示出强的活性。

项目成果

M. Tanaka, T. Ichiki, M. Oba, and H. Suemune,: "Solid-State Conformation of a Hybrid Tripeptide Between β-Amino Acid; 8-Aminocyclooct-4-enecarboxylic Acid and 2-Aminoisobutyric Acid"Chem. Pharm. Bull.. 49(9). 1178-1181 (2001)

M. Tanaka、T. Ichiki、M. Oba 和 H. Suemune，“β-氨基酸、8-氨基环辛-4-烯甲酸和 2-氨基异丁酸之间的混合三肽的固态构象”，Pharm。 . 公牛.. 1178-1181 (2001)。

M.Kurihara: "Computational study on conformation of oligopeptides containing chiral α,α-disubstituted amino acids"Peptides 2002. 786-787 (2003)

M.Kurihara：“含有手性α,α-二取代氨基酸的寡肽构象的计算研究”Peptides 2002. 786-787 (2003)

M. Oba, M. Tanaka, M. Kurihara, and H. Suemune,: "Conformation of Peptides Containing a Chiral α-Ethylated α,α-Disubstituted α-Amino Acid: (S)-αEthylleucine (=(2S)-2-Amino-2-ethyl-4-methylpentanoic Acid) within Sequences of Dimethylglycine and Diethylglyc

M. Oba、M. Tanaka、M. Kurihara 和 H. Suemune，：“含有手性 α-乙基化 α,α-二取代 α-氨基酸的肽的构象：(S)-α 乙基亮氨酸 (=(2S)-2 -氨基-2-乙基-4-甲基戊酸）在二甲基甘氨酸和二乙基甘氨酸的序列中

M.Oba: "Conformation of Peptides Containing a Chiral α-Ethylated α,α-Disubstituted α-Amino Acid: (S)-αEthylleucine (= (2S)-2-Amino-2-ethyl-4-methylpentanoic Acid) within Sequences of Dimethylglycine and Diethylglycine Residues"Helvetica Chimica Acta. 85(1

M.Oba：“序列中含有手性 α-乙基化 α,α-二取代 α-氨基酸的肽的构象：(S)-α 乙基亮氨酸（= (2S)-2-氨基-2-乙基-4-甲基戊酸）二甲基甘氨酸和二乙基甘氨酸残基的测定”Helvetica Chimica Acta. 85(1

M.Oba: "Conformational Study of Peptides Containing (S)-Ethylleucine as a Chiral α,α-Disubstituted Amino Acid"Peptides 2002. (In press). (2003)

M.Oba：“含有 (S)-乙基亮氨酸作为手性 α,α-二取代氨基酸的肽的构象研究”肽 2002 年。（出版中）。