Tsubery H, Ofek I, Cohen S, Fridkin M
Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Peptides. 2001 Oct;22(10):1675-81. doi: 10.1016/s0196-9781(01)00503-4.
Polymyxin B (PMB) is a potent antibacterial lipopeptide composed of a positively charged cyclic peptide ring and a fatty acid containing tail. Polymyxin B nonapeptide (PMBN), the deacylated amino derivative of polymyxin B, is much less bactericidal but able to permeabilize the outer membrane of Gram-negative bacteria and to neutralize the toxic effects of lipopolysaccharide (LPS). In this study, we synthesized and evaluated the antibacterial and LPS neutralizing activities of four PMBN analogs modified at their N-terminal. Our results suggest that oligoalanyl substitutions of PMBN do not effect most of PMBN activities. However, a hydrophobic aromatic substitution generated a PMB-like molecule with high antibacterial activity and significant reduced toxicity.
多粘菌素B（PMB）是一种强效抗菌脂肽，由带正电荷的环状肽环和含脂肪酸的尾部组成。多粘菌素B九肽（PMBN）是多粘菌素B的脱酰基氨基衍生物，杀菌作用弱得多，但能够使革兰氏阴性菌的外膜通透性增加，并中和脂多糖（LPS）的毒性作用。在本研究中，我们合成并评估了四种在N端修饰的PMBN类似物的抗菌和LPS中和活性。我们的结果表明，PMBN的寡丙氨酰取代不会影响其大部分活性。然而，疏水性芳香取代产生了一种具有高抗菌活性且毒性显著降低的类似PMB的分子。
