Polymyxin B: an ode to an old antidote for endotoxic shock.
Polymyxin B: an ode to an old antidote for endotoxic shock.
复制标题
多粘菌素 B：对一种古老的内毒素休克解毒剂的颂歌。
作者：
V. Bhor;C. Thomas;N. Surolia;A. Surolia
内毒素休克是一种以血液动力学紊乱、凝血异常和多系统器官衰竭为特征的综合征，由脂多糖（LPS）释放到循环中引起，脂多糖是革兰氏阴性细菌外膜的结构多样性组分，并且是导致人类60%死亡率的原因。多粘菌素B（PMB）是一种环状阳离子肽类抗生素，可中和内毒素，但在此过程中会引起严重的副作用。然而，PMB有效的内毒素中和能力为设计用于对抗内毒素中毒的无毒治疗剂提供了可能性。在对抗内毒素休克的众多方法中，肽介导的LPS中和似乎是最有吸引力的一种。PMB与LPS结合的精确模式和其中涉及的结构特征仅在最近使用各种生物物理方法才得以阐明。这些表明PMB对内毒素的有效中和不是仅仅通过与LPS结合来实现的，而是需要将其从膜上隔离。将这一特性纳入内毒素中和肽的设计中，将有助于开发内毒素休克的有效解毒剂。
Endotoxic shock, a syndrome characterized by deranged hemodynamics, coagulation abnormalities, and multiple system organ failure is caused by the release into the circulation of lipopolysaccharide (LPS), the structurally diverse component of Gram-negative bacterial outer membranes, and is responsible for 60% mortality in humans. Polymyxin B (PMB), a cyclic, cationic peptide antibiotic, neutralizes endotoxin but induces severe side effects in the process. The potent endotoxin neutralizing ability of PMB, however, offers possibilities for designing non-toxic therapeutic agents for combating endotoxicosis. Amongst the numerous approaches for combating endotoxic shock, peptide mediated neutralization of LPS seems to be the most attractive one. The precise mode of binding of PMB to LPS and the structural features involved therein have been elucidated only recently using a variety of biophysical approaches. These suggest that efficient neutralization of endotoxin by PMB is not achieved by mere binding to LPS but requires its sequestration from the membrane. Incorporation of this feature into the design of endotoxin neutralizing peptides should lead to the development of effective antidotes for endotoxic shock.
DOI：
10.1016/s0021-9258(18)68262-6
发表时间：
1988-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Tobias;J. Mathison;R. Ulevitch
通讯作者：
P. Tobias;J. Mathison;R. Ulevitch
影响因子：
7
作者：
P. Elsbach;Jerrold Weiss
通讯作者：
P. Elsbach;Jerrold Weiss
DOI：
10.1073/pnas.90.10.4733
发表时间：
1993-05-15
影响因子：
11.1
作者：
PEREIRA, HA;ERDEM, I;SPITZNAGEL, JK
通讯作者：
SPITZNAGEL, JK