Synthetic study of peptide neurotoxins isolated from animals in South East Asia

从东南亚动物中分离的肽神经毒素的合成研究

• 批准号: 15550151
• 负责人: SATO Kazuki
• 金额: $ 2.37万
• 依托单位: Fukuoka Women's University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15550151/
• 关键词: peptide neurotoxin; ion channel; cone snail; conotoxin; scorpion toxin; peptide synthesis; South East Asia; disulfide bond pattern

(1)Synthesis and disulfide pairing determination of novel conotoxins from cone snail.We synthesized three novel conotoxins CMrII, CMrIII, and CMrV isolated from Cones marmoreus. All of them have three intramolecular disulfide bonds. In order to determine the disulfide pairings, we synthesized CMrII by selective two-step disulfide bond formation method. HPLC co-elution with native peptide suggested that CMrII has C1-C4, C2-C5, and C3-C6 combinations. Whereas, it was suggested that CMrV has different disulfide patterns. Re-examination is in progress for CMrV.Four novel conotoxins, AmIV, AmVIIA, AmVIIB, and AmIX were isolated from C. amadis by foreign collaborators. Both C-terminal amidated and free peptides were synthesized for AmIV and AmIX. HPLC co-elution indicated that AmIV and AmIX had free and amidated C-terminals, respectively. AmVIIA and AmVIIB were synthesized and shown to have free C-terminals.(2)Relationships of disulfide pattern, three-dimensional structure and activity of sc … More orpion toxins.Hefutoxin-1 isolated from scorpion Heterometrus fuIvipes adopts a unique three-dimensional fold of two parallel helices linked by two disulfide bridges without any βsheets. We synthesized two analogs of hefutoxin-1 with deletion of one or two amino acid residues at the central loop region. Enzymatic digestion of deletion analogs showed that both of them have the same disulfide pairings as native peptides. Several analogs with amino acid substitution were synthesized for structure-activity relationship study.Five novel peptide toxins HS2388, HS2404, HS2620, HS3019, and HS3700 were isolated from scorpion H, spinifer venom. We synthesized all of them and confirmed that HS2388 and HS2404 have amidated C-terminals, whereas others have free C-terminals. Comparison of CD spectra and enzymatic digestion suggested that HS2388, HS2404, HS2620, and HS3019 have the same disulfide pattern as that of hefutoxin-1. Synthetic analogs of HS2620 suggested that the basic residue at the 20th position interfere the interaction of this toxin to K channels. Less

（1）从锥卡中的新型综合毒素的合成和二硫化配对确定。我们合成了从锥体Marmoreus分离出的三种新型综合毒素CMRII，CMRIII和CMRV。它们都有三个分子内二硫键。为了确定二硫键配对，我们通过选择性两步二硫键形成方法合成CMRII。 HPLC与天然肽的共同布置表明CMRII具有C1-C4，C2-C5和C3-C6组合。鉴于，建议CMRV具有不同的二硫化模式。 CMRV的重新审查正在进行中。 C末端胺化和自由胡椒剂均合成用于AMIV和AMIX。 HPLC共同精确表明，AMIV和AMIX分别具有自由和胺化的C末端。合成了AMVIIA和AMVIIB，并证明具有游离C末端。（2）二硫键模式，SC的三维结构和SC的活性的关系……更多的ORPION毒素.hefutoxin.hefutoxin.hefutoxin-与Scorpion Heterometrus fuivipes中的hefutoxin-1相互链接，从而在两个平行的螺旋范围内链接了两次混乱。我们在中央环区域中合成了两个或两个氨基酸的Hefutoxin-1类似物。缺失类似物的酶促消化表明，它们俩的二硫键配对与天然肽的二硫键配对相同。合成了几种与氨基酸取代的类似物进行结构 - 活性关系研究。新型肽毒素HS2388，HS2404，HS2620，HS3019和HS3700从Spinifer Venom中分离出来。我们的HS2620合成类似物表明，第20位的基本居住地干扰了这种毒素与K通道的相互作用。较少的

项目成果

Assignment of voltage-gated potassium channel blocking activity to κ-KTx1.3, a non-toxic homologue of κ-hefutoxin-1, from Heterometrus spinifer venom

• DOI: 10.1016/j.bcp.2004.10.018
• 发表时间: 2005-02-15
• 期刊: BIOCHEMICAL PHARMACOLOGY
• 影响因子: 5.8
• 作者: Nirthanan, S;Pil, J;Tytgat, J
• 通讯作者: Tytgat, J

Novel interactions identified between μ-conotoxin and the Na^+ channel Domain I P-loop : Implications for toxin-pore binding geometry

μ-芋螺毒素和 Na^+ 通道之间发现的新相互作用 结构域 I P 环：对毒素-孔结合几何结构的影响

• 发表时间: 2003
• 期刊: Biochem.J. 85
• 作者: Xue;T.
• 通讯作者: T.

Conticello, S.G.: "The pro-domain of a secreted hydrophobic mini-protein facilitates its export from the endoplasmic reticulum by hitchhiking on sorting receptors"J.Biol.Chem.. 278. 26311-26314 (2003)

Conticello, S.G.：“分泌型疏水性微型蛋白的前结构域通过搭上分选受体的便车，促进其从内质网的输出”J.Biol.Chem.. 278. 26311-26314 (2003)

Adenosine A_1-receptor-mediated tonic inhibition of glutamate release at rat hippocampal Ca3-CA1 synapses in primarily due to inhibition of N-type Ca^<2+> channels.

腺苷A_1受体介导的大鼠海马Ca 3 -CA 1 突触谷氨酸释放的强直性抑制主要是由于N型Ca 2+ 通道的抑制。

• 发表时间: 2004
• 期刊: Fur.J.Pharmacol. 499
• 作者: Manita;S.;Kawamura;Y.;Sato;K.;Inoue;M.;Kudo;Y.;Miyakawa.;H.
• 通讯作者: H.

Novel interactions identified between μ-conotoxin and the Na^+ channel Domain IP-loop : Implications for toxin-pore binding geometry.

μ-芋螺毒素和 Na^+ 通道域 IP 环之间发现的新相互作用：对毒素-孔结合几何结构的影响。

• 发表时间: 2003
• 期刊: Biophysical J. 85
• 作者: Xue;T.;Ennis;I.L.;Sato;K.;French;R.J.;Li;R.A.
• 通讯作者: R.A.