Phillips N C, Chedid L
Infect Immun. 1987 Jun;55(6):1426-30. doi: 10.1128/iai.55.6.1426-1430.1987.
Two muramyl dipeptides, N-acetylmuramyl-L-alanyl-D-isoglutamine and its adjuvant-inactive isomer N-acetylmuramyl-D-alanyl-D-isoglutamine, were examined for their ability to protect mice carrying the CBA/N immune deficiency gene (xid) against lethal bacterial challenge. Prophylactic treatment with N-acetylmuramyl-L-alanyl-d-isoglutamine gave significant protection against Streptococcus pneumoniae, Salmonella typhimurium, and Salmonella enteritidis infection. N-Acetylmuramyl-D-alanyl-D-isoglutamine was unable to confer protection. Incorporation of the lipophilic glycerol dipalmitate derivatives of the two muramyl dipeptides within liposomal carriers resulted in a significant enhancement of anti-infectious activity, both with respect to number of survivors and length of survival. Liposomal muramyl dipeptides were 10- to 15-fold more potent than free muramyl dipeptide; enhanced potency was most evident with N-acetylmuramyl-D-alanyl-D-isoglutamine. Prophylactic treatment with liposomes containing the lipophilic muramyl dipeptides resulted in enhanced clearance of bacteria from the blood (greater than 3-fold increase in rate) when compared with that of hydrosoluble N-acetylmuramyl-L-alanyl-D-isoglutamine, indicating a correlation between reticuloendothelial stimulation and anti-infectious activity.
研究了两种胞壁酰二肽，N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺及其无佐剂活性的异构体N-乙酰胞壁酰-D-丙氨酰-D-异谷氨酰胺，对携带CBA/N免疫缺陷基因（xid）的小鼠抵抗致死性细菌攻击的保护能力。用N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺进行预防性治疗，可对肺炎链球菌、鼠伤寒沙门氏菌和肠炎沙门氏菌感染提供显著保护。N-乙酰胞壁酰-D-丙氨酰-D-异谷氨酰胺无法提供保护。将两种胞壁酰二肽的亲脂性甘油二棕榈酸酯衍生物掺入脂质体载体中，在存活小鼠数量和存活时间方面，均显著增强了抗感染活性。脂质体胞壁酰二肽的效力比游离胞壁酰二肽高10至15倍；N-乙酰胞壁酰-D-丙氨酰-D-异谷氨酰胺的增强效力最为明显。与水溶性N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺相比，用含有亲脂性胞壁酰二肽的脂质体进行预防性治疗，可使血液中细菌的清除率提高（速率增加超过3倍），这表明网状内皮系统刺激与抗感染活性之间存在相关性。
