Yonezawa H, Okamoto K, Kaneda M, Tominaga N, Izumiya N
Int J Pept Protein Res. 1983 Nov;22(5):573-81. doi: 10.1111/j.1399-3011.1983.tb02131.x.
The antibiotic gramicidin S (GS) has the structure of cyclo (-L-Val1-L-Orn2-L-Leu3-D-Phe4-L-Pro5-L-Val1'-L-Orn2'-L-Leu3'-D-Phe4'-L-Pro5'-) and is basic in character. Five GS analogs including [Gly1,1']-GS and the neutral [L-Hnv2,2']-GS (Hnv represents delta-hydroxynorvaline) were synthesized by the solid-phase method to evaluate the role of L-Val1,1' and L-Orn2,2' residues in GS. The hybrid analogs [( Gly1]-GS and [L-Hnv2]-GS) and [D-Tyr4,4']-GS showed high antibacterial activities, whereas [Gly1,1']-GS and [L-Hnv2,2']-GS possessed no activity. Inhibitory effects by these analogs for the adsorption of 14C-labeled GS on cells of bacteria sensitive to GS were determined. The structure-activity relationship of GS is discussed on the basis of the results on these GS analogs.
抗生素短杆菌肽S（GS）具有环（-L-缬氨酸1-L-鸟氨酸2-L-亮氨酸3-D-苯丙氨酸4-L-脯氨酸5-L-缬氨酸1'-L-鸟氨酸2'-L-亮氨酸3'-D-苯丙氨酸4'-L-脯氨酸5'-）的结构，呈碱性。通过固相法合成了包括[甘氨酸1,1']-GS和中性的[L-δ-羟基正缬氨酸2,2']-GS（Hnv代表δ-羟基正缬氨酸）在内的五种GS类似物，以评估GS中L-缬氨酸1,1'和L-鸟氨酸2,2'残基的作用。杂合类似物[（甘氨酸1）-GS和[L-δ-羟基正缬氨酸2]-GS]以及[D-酪氨酸4,4']-GS表现出高抗菌活性，而[甘氨酸1,1']-GS和[L-δ-羟基正缬氨酸2,2']-GS没有活性。测定了这些类似物对14C标记的GS吸附到对GS敏感的细菌细胞上的抑制作用。基于这些GS类似物的结果讨论了GS的构效关系。
