Membrane Protein Recognition by Ladder-shaped Polyether Compounds

梯形聚醚化合物的膜蛋白识别

• 批准号: 08458171
• 负责人: MURATA Michio
• 金额: $ 3.07万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08458171/
• 关键词: polyether compounds; membrane proteins; maitotoxin; ciguatoxin; ガングリオシド; 赤血球膜

Marine microalgae are known to be arich source of structurally and biologically intriguing polyketides. Among those, maitotoxin (MTX) attracts attention of chemists and biochemists since the toxin possesses the largest molecular weight of 3422 Da among secondary metabolites and very potent lethality (50 ng/kg, mice, ip.). Its structure has been determined by combined use of NMR,MS/MS and synthetic chemistry. A new method based on carbon-proton spin coupling (2,3JC,H) was introduced for the configurational determination of the acyclic sidechains. Based on these data, the stereostructure of the whole molecule has been elucidated, which sheds light on its molecular mode of action. Recent findings suggest that MTX recognaizes its taget protein with the hydrophobic polycyclic ethers (the upper half of the structure), which probably interacts with the transmembrane portion of the protein.

众所周知，海洋微藻是结构和生物学上有趣的聚酮化合物的丰富来源。其中，maitotoxin （MTX）因其在次生代谢物中分子量最大，达3422 Da，具有极强的致死率（50 ng/kg，小鼠，ip.）而受到化学家和生化学家的关注。通过核磁共振、质谱联用和合成化学等手段对其结构进行了测定。介绍了一种基于碳质子自旋耦合（2,3jc，H）的非环侧链构型测定新方法。基于这些数据，整个分子的立体结构已被阐明，从而揭示了其分子作用方式。最近的研究结果表明，MTX通过疏水多环醚（结构的上半部分）识别其目标蛋白，这可能与蛋白质的跨膜部分相互作用。

项目成果

Nobuaki Matsumori: "Long-range carbon-proton conpling constants for steereochemical assginment of acyclic Structures in natural products." Tetrahedron Letter. 37. 1269-1272 (1996)

Nobuaki Matsumori：“用于天然产物中无环结构立体化学分配的长程碳-质子配对常数。”

K, Konoki.: "Blockade of MTX-induced Ca^<2+> in rat glioma C_6 alls by alhylamines" Journal of Natural Toxins. 5. 209-217 (1996)

K，Konoki.：“大鼠神经胶质瘤C_6中MTX诱导的Ca ^ 2 的阻断全部由乙胺胺完成”，天然毒素杂志。

T.Nonomura.: "The complete structure of maitotocin IIi Scereochemistry of the C135-C142 sidu chain and the absolute mfihuratlm of the entiremolecule" Angewandle Chemie,International Edition in English. 35. 1675-1678 (1996)

T.Nonomura.：“C135-C142 sidu链的maitotocin IIIi Scereochemistry和整个分子的绝对mfihuratlm的完整结构”Angewandle Chemie，国际版英文。

K.Konoki.: "Inhibition of maitotoxin-induced C_a^<2+> in fhex in rat glioma C_6 cells by breretoxing and sythetil fragments of maitoroxin." Jounal of Neurochemistry. 70. 409-416 (1998)

K.Konoki.：“通过breretoxing和maitoroxin的合成片段抑制大鼠神经胶质瘤C_6细胞中maitotoxin诱导的C_a^2。”

Makoto Sasaki: "The complete structure of maitotoxin I ; Stereochemstry of the C1-C14 side chain." Angewandte Chemie, International Edition in English. 35. 1672-1675 (1996)

Makoto Sasaki：“麦芽毒素 I 的完整结构；C1-C14 侧链的立体化学。”