ALL-D AMINO ACID-CONTAINING CHANNEL-FORMING ANTIBIOTIC PEPTIDES
ALL-D AMINO ACID-CONTAINING CHANNEL-FORMING ANTIBIOTIC PEPTIDES
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DOI：
10.1073/pnas.87.12.4761
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发表时间：
1990-06-01
影响因子：
11.1
通讯作者：
MERRIFIELD, RB
中科院分区：
文献类型：
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作者：
WADE, D;BOMAN, A;MERRIFIELD, RB
合成了三种天然抗菌药物天蚕素A、爪蟾抗菌素2酰胺和蜂毒肽的D对映体。此外，还合成了两个天蚕素-蜂毒素嵌合杂合肽的D对映体。每一个D异构体所示的圆二色性是一个镜像的相应的L异构体在几种溶剂的混合物。在20%六氟-2-丙醇中，肽含有43-75%的α-螺旋。全D肽对酶促降解具有抗性。在平面脂质双层的肽产生单通道电导，和D和L对映异构体引起等量的电导率。所有的肽是有效的抗菌剂对代表性的革兰氏阴性和革兰氏阳性物种。每个肽对的D和L对映体在实验误差内具有相同的活性。绵羊红细胞被D-和L-蜂毒肽裂解，但不被天蚕素A的异构体、爪蟾抗菌肽2酰胺或天蚕素A-（1-13）-蜂毒肽-（1 - 13）-NH 2或天蚕素A-（1-8）-蜂毒肽-（1- 1 - 8）-NH 2的杂交体裂解。血液形式的疟疾寄生虫恶性疟原虫的感染性也被D和L杂交抑制。有人建议，这些肽对细菌，红细胞，疟原虫，和人造脂质双层膜的作用模式可能是相似的，并涉及跨越膜的离子通道孔的形成，但没有特定的相互作用与手性受体或酶。
The D enantiomers of three naturally occurring antibiotics-cecropin A, magainin 2 amide, and melitin.sbd.were synthesized. In addition, the D enantiomers of two synthetic chimeric cecropin-melittin hybrid peptides were prepared. Each D isomer was shown by circular dichroism to be a mirror image of the corresponding L isomer in several solvent mixtures. In 20% hexafluoro-2-propanol the peptides contained 43-75% .alpha.-helix. The all-D peptides were resistant to enzymatic degradation. The peptides produced single-channel conductances in planar lipid bilayers, and the D and L enantiomers caused equivalent amounts of electrical conductivity. All of the peptides were potent antibacterial agents against representative Gram-negative and Gram-positive species. The D and L enantiomers of each peptide pair were equally active, within experimental error. Sheep erythrocytes were lysed by both D- and L-melittin but not by either isomer of cecropin A, magainin 2 amide, or the hybrids cecropin A-(1-13)- melittin-(1-13)-NH2 or cecropin A-(1-8)-melittin-(1-18)-NH2. The infectivity of the bloodstream form of the malaria parasite Plasmodium falciparum was also inhibited by the D and L hybrids. It is suggested that the mode of action of these peptides on the membranes of bacteria, erythrocytes, plasmodia, and artifical lipid bilayers may be similar and involves the formation of ion-channel pores spanning the membranes, but without specific interaction with chiral receptors or enzymes.