STIMULATION OF NONSPECIFIC RESISTANCE TO INFECTION INDUCED BY MURAMYL DIPEPTIDE ANALOGS SUBSTITUTED IN THE GAMMA-CARBOXYL GROUP AND EVALUATION OF N-ALPHA-MURAMYL DIPEPTIDE-N-EPSILON-STEAROYLLYSINE
STIMULATION OF NONSPECIFIC RESISTANCE TO INFECTION INDUCED BY MURAMYL DIPEPTIDE ANALOGS SUBSTITUTED IN THE GAMMA-CARBOXYL GROUP AND EVALUATION OF N-ALPHA-MURAMYL DIPEPTIDE-N-EPSILON-STEAROYLLYSINE
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DOI：
10.1128/iai.39.3.1029-1040.1983
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发表时间：
1983-01-01
影响因子：
3.1
通讯作者：
AZUMA, I
中科院分区：
文献类型：
--
作者：
MATSUMOTO, K;OTANI, T;AZUMA, I
刺激由在γ-谷氨酰胺中具有取代功能的胞壁酰二肽（MDP）类似物诱导的抗感染性在小鼠实验性大肠杆菌感染中检测了D-异谷氨酰残基的羧基。一种MDP类似物，其是抗感染的有效增强剂，MDP-N ε-硬脂酰赖氨酸[MDP-Lys（L18）]，是通过对3类化合物的比较评估而选择的：烷基酰胺，γ-酯和N α- MDP-N ε-酰基赖氨酸衍生物。以MDP为对照，从细菌学角度评价了MDP-Lys（L18）的抗感染活性。研究了MDP-Lys（L18）对小鼠对各种微生物感染的易感性的影响。对大肠杆菌的保护活性最大。大肠杆菌和葡萄球菌感染，对假单胞菌和念珠菌感染相当，对克雷伯菌感染最少。研究了细菌接种量和MDP处理时间、剂量和给药途径对保护活性的影响。MDP-Lys（L18）在所有给药途径（甚至口服）的保护试验中均证明了其有效性。接种量的影响较小，诱导保护活性所需的最小剂量值特别小，证实了其高效力。在用类似物处理并感染大肠杆菌的小鼠的血液和器官中观察到细菌存活的减少。杆菌获得了以下两个有用的效果：糖肽和化疗药物的协同作用和刺激免疫功能低下的动物对感染的抵抗力。
Stimulation of resistance to infection induced by the analogs of muramyl dipeptide (MDP) having substituted functions in the .gamma.-carboxyl group of D-isoglutamyl residue was examined in experimental Escherichia coli infections in mice. An MDP analog which is an efficient strengthener of resistance to infection, N.alpha.-MDP-N.epsilon.-stearoyllysine [MDP-Lys(L18)], was selected through the comparative assessment of a number of compounds in 3 categories: .gamma.-alkylamides, .gamma.-esters and N.alpha.-MDP-N.epsilon.-acyllysine derivatives. The antiinfectious activity of MDP-Lys(L18) was evaluated bacteriologically in comparison with that of MDP. The effect of MDP-Lys(L18) on the susceptibility of mice to infections with various microorganisms was studied. Protective activity was greatest against E. coli and Staphylococcus infections, considerable against Pseudomonas and Candida infections, and least against Klebsiella infection. The effects of bacterial inoculum size and MDP treatment timing, dose and route of administration on protective activity were studied. The efficacy of MDP-Lys(L18) in protection tests was demonstrated for all administration routes, even oral. Its high potency was confirmed by the smaller influence of inoculum size and the particularly small value of the minimum dosage required for inducing protective activity. A decrease in bacterial survival was observed in the blood and organs of mice treated with the analog and infected with E. coli. The following 2 useful effects were obtained: the synergistic effect of glycopeptide and chemotherapeutic agents and the stimulation of resistance to infection in animals immunocompromised by cyclophosphamide treatment.