Synthetic polymer antigen having an epitope peptide for development of malaria vaccine

用于开发疟疾疫苗的具有表位肽的合成聚合物抗原

• 批准号: 14350481
• 负责人: KATAKAI Ryoichi
• 金额: $ 9.41万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14350481/
• 关键词: Plasmodium falciparum; enolase; epitope; peptide; acrloyl polymer; synthesis; ELISA; synthetic polymer antigen; メタクリロイルポリマー; ペプチト; 構造-抗原活性相関; デンドリマー

An enolase produced by Plasmodium falciparum has been found to be highly reactive immunologically to the sera of falciparum malaria patients. A 16-peptide sequence GlyPheAlaProAsnIleLeuAsnAlaAsnGluAlaLeuAspLeuLeu named GL16 in the enolase has been determined to be an epitope. We have synthesized a polymeric antigen containing the epitope GL16 to make a synthetic malaria vaccine.The peptide designed have a C-terminal extension tetraglutamic moiety to improve the solubility and N-terminal 6-aminohexamethylene carboxylic acid residue as a linker to the polymer main chain. The peptide was synthesized by the fragment condensation procedure in the solution. Four fragments of the GL16-EEEE peptide were prepared by the stepwise procedure. The N-terminal amino group in 6-aminohexamethylene carbonyl GL16-EEEE was allowed to react with acryloyl chloride to give a monomer. The monomer takes an α-helical conformation in hydrophilic solvent system. The monomer was copolymerized with methacrylamide (1.95wt%) in dimethylsulfoxide by γ-ray irradiation. The antigenic activity of the polymer thus obtained was analyzed by the ELISA method. The result of the ELISA has shown that the polymeric antigen has 1.8 times stronger RFU value for the malaria patients'sera than that for the healthy volunteers.

已发现恶性疟原虫产生的烯醇化酶对恶性疟疾患者的血清具有高度免疫反应性。烯醇化酶中命名为GL 16的16肽序列GlyPheAlaProAsnIleLeuAsnAlaAsnGluAlaLeuAspLeuLeu已被确定为表位。我们合成了一种含有表位GL 16的多聚体抗原，该抗原的C端有一个四谷氨酸的延伸部分，以提高其溶解性，N端有一个6-氨基-N-羧酸残基作为连接基团。在溶液中通过片段缩合程序合成肽。通过逐步程序制备GL 16-EEEE肽的四个片段。使6-氨基双羰基GL 16-EEEE中的N-末端氨基与丙烯酰氯反应以得到单体。单体在亲水性溶剂体系中呈α-螺旋构象。在二甲基亚砜溶剂中，以1.95wt%的甲基丙烯酰胺为引发剂，采用γ-射线辐照法进行共聚反应。通过ELISA方法分析由此获得的聚合物的抗原活性。ELISA结果表明，该多聚体抗原对疟疾病人血清的RFU值比对健康人血清的RFU值高1.8倍。

项目成果

Synthetic Study of an Antigenic Peptide Having a Partial Sequence of Plasmodium falciparum Enolase

具有恶性疟原虫烯醇酶部分序列的抗原肽的合成研究

• 发表时间: 2005
• 期刊: Peptide Science 2004
• 作者: K.Omi;K.Kuriyama;K.Yamada;H.Oku;S.Kano;M.Suzuki;R.Katakai
• 通讯作者: R.Katakai

Computational Analysis in the Study of Antigenic Determinants in an Enolase Molecule from Plasmodium falciparum

恶性疟原虫烯醇化酶分子抗原决定簇研究中的计算分析

• 发表时间: 2003
• 期刊: Forum Cheju-8, Proceedings of the 8-th Japan-Korea Parasitologists' seminar
• 作者: H.Oku;T.Ishiguro;K.Sato;S.Kano;M.Suzuki;H.Yamamoto;N.Ueyama;K.Yamada;R.Katakai
• 通讯作者: R.Katakai

H.Oku, H.Suzuki, K.Yamada, R.Katakai: "Synthesis and Properties of Trans-Membrne Sequences from Plasmodium falciparum Chloroquine Resistant transporter Protein (PfCRT)"Peptide Science 2003. 367-370 (2004)

H.Oku、H.Suzuki、K.Yamada、R.Katakai：“恶性疟原虫氯喹抗性转运蛋白 (PfCRT) 跨膜序列的合成和特性”肽科学 2003. 367-370 (2004)

Synthetic Study of an Antigenic Peptide Having a Partial Sequence of Plasmodium, falciparum Enolase

具有疟原虫烯醇化酶部分序列的抗原肽的合成研究

• 发表时间: 2005
• 期刊: Peptide Science 2004
• 作者: K.Omi;K.Kuriyama;K.Yamada;H.Oku;S.Kano;M.Suzuki;R.Katakai
• 通讯作者: R.Katakai

Synthetic Study of an Antigenic Peptide Having a Partial Sequence of Plasmododium falciparum Enolase

具有恶性疟原虫烯醇酶部分序列的抗原肽的合成研究

• 发表时间: 2004
• 期刊: Peptide Science
• 影响因子: 2.4
• 作者: K.Omi;K.Kuriyama;K.Yamada;H.Oku;S.Kano;K.Sato;M.Suzuki;R.Katakai
• 通讯作者: R.Katakai