ITURINS, A SPECIAL-CLASS OF PORE-FORMING LIPOPEPTIDES - BIOLOGICAL AND PHYSICOCHEMICAL PROPERTIES
ITURINS, A SPECIAL-CLASS OF PORE-FORMING LIPOPEPTIDES - BIOLOGICAL AND PHYSICOCHEMICAL PROPERTIES
复制标题
DOI：
10.1016/0300-483x(94)90159-7
复制
发表时间：
1994-02-28
期刊：
影响因子：
4.5
通讯作者：
PEYPOUX, F
中科院分区：
文献类型：
--
作者：
MAGETDANA, R;PEYPOUX, F
Iturins 是从各种枯草芽孢杆菌菌株的培养基中提取的脂肽家族。这些两亲性化合物的特征在于由七个氨基酸残基组成的肽环，其中包括不变的 D-Tyr2，其恒定手性序列 LDDLLDL 由 C-14-C-17 脂肪族 β-氨基酸封闭。它们对多种致病酵母和真菌表现出很强的抗真菌活性，但其抗菌活性仅限于某些细菌，例如藤黄微球菌。伊枯草菌素脂肽的生物活性由肽循环的一级结构调节，如 D-Tyr2 残基的甲基化（其活性显着降低）或通过两个相邻的 Ser6-Asn 7 残基的倒置（这使得枯草菌素比伊枯草菌素 A 更活性）来调节。抗真菌活性与伊枯草菌素脂肽与伊枯草菌素的相互作用有关。 靶细胞的细胞质膜，其K+通透性大大增加。伊枯草菌素化合物增加膜细胞通透性的能力是由于离子传导孔的形成，其特性取决于膜的脂质组成和肽循环的结构。单层实验表明，这些离子孔是磷脂膜中存在聚集体（脂肽聚集体或脂肽/磷脂复合物聚集体）的结果。还表明，当活跃时，伊枯草菌素与甾醇强烈相互作用，形成脂肽/胆固醇复合物。因此，生物有效的结构可能是三元结构：伊枯草菌素/磷脂/甾醇。
Iturins are a family of lipopeptides extracted from the culture media of various strains of Bacillus subtilis. These amphiphilic compounds are characterized by a peptide ring of seven amino acid residues including an invariable D-Tyr2, with the constant chiral sequence LDDLLDL closed by a C-14-C-17 aliphatic beta-amino acid. They exhibit strong antifungal activities against a wide variety of pathogenic yeasts and fungi but their antibacterial activities are restricted to some bacteria such as Micrococcus luteus. The biological activity of the iturin lipopeptides is modulated by the primary structure of the peptide cycle as illustrated by the methylation of the D-Tyr2 residue which dramatically decreases the activity or by the inversion of the two adjacent Ser6-Asn 7 residues which makes mycosubtilin more active than iturin A. The antifungal activity is related to the interaction of the iturin lipopeptides with the cytoplasmic membrane of target cells, the K+ permeability of which is greatly increased. The ability of iturin compounds to increase the membrane cell permeability is due to the formation of ion-conducting pores, the characteristics of which depend both on the lipid composition of the membrane and on the structure of the peptide cycle. From monolayer experiments it has been suggested that these ionic pores are the consequence of the presence of aggregates (lipopeptide aggregates or lipopeptide/phospholipid complex aggregates) in the phospholipid membrane. It has also been shown that, when active, iturins interact strongly with sterols, forming lipopeptide/cholesterol complexes. Therefore, the biologically efficient structure might be a ternary structure: iturin/phospholipid/sterol.