Volpon L, Besson F, Lancelin J M
Laboratoire de RMN Biomoléculaire associé au CNRS, Université Claude Bernard, Lyon 1, Villeurbanne, France.
FEBS Lett. 2000 Nov 17;485(1):76-80. doi: 10.1016/s0014-5793(00)02182-7.
Plipastatins A and B are antifungal antibiotics belonging to a family of lipopeptides capable of inhibiting phospholipase A(2) (PLA(2)) and are biosynthesised under certain circumstances by Bacillus subtilis. U-(15)N plipastatins A and B were obtained from cultures of the strain NCIB 8872 on a Landy medium modified for stable-isotope labelling by the substitution of the L-glutamic acid used as the sole nitrogen source, by (15)NH(4)Cl. These two lipo-decapeptides, lactonised by esterification of the Ile10 C-terminus with the phenolic hydroxyl of Tyr3, differ only by a D-Ala (plipastatin A)/D-Val (plipastatin B) substitution at the position 6. The (1)H- and (15)N-nuclear magnetic resonance (NMR) signals of a 4:6 mixture of plipastatins A and B were unambiguously assigned and their structures in dimethylsulfoxide solution were calculated on the basis of a set of NMR-derived restraints. Plipastatins A and B are well-defined structures in solution stabilised by a type 1 beta-turn comprising residues 6-9 and several other specific hydrogen bonds. The structures afford a first molecular basis for the future studies of their biological activities both in lipidic layers or on PLA(2).
普利他汀A和B是一类脂肽类抗真菌抗生素，能够抑制磷脂酶A(2)（PLA(2)），在特定条件下由枯草芽孢杆菌生物合成。U-(15)N标记的普利他汀A和B是通过用(15)NH(4)Cl替代用作唯一氮源的L-谷氨酸，从NCIB 8872菌株在经修饰用于稳定同位素标记的Landy培养基上的培养物中获得的。这两种脂十肽通过Ile10 C末端与Tyr3的酚羟基酯化而内酯化，仅在第6位存在D-Ala（普利他汀A）/D-Val（普利他汀B）的取代差异。明确归属了普利他汀A和B的4:6混合物的(1)H和(15)N核磁共振（NMR）信号，并基于一组NMR衍生的限制条件计算了它们在二甲亚砜溶液中的结构。普利他汀A和B在溶液中具有明确的结构，由包含第6 - 9位残基的1型β-转角和其他几个特定氢键稳定。这些结构为未来研究它们在脂质层或PLA(2)上的生物活性提供了首个分子基础。
