Chedid L, Parant M, Parant F, Audibert F, Lefrancier F, Choay J, Sela M
Proc Natl Acad Sci U S A. 1979 Dec;76(12):6557-61. doi: 10.1073/pnas.76.12.6557.
N-Acetylmuramyl-L-Ala-D-Glu-NH2 (muramyl dipeptide) and several of its derivatives are effective immunoactivators that can enhance nonspecific resistance to infection but can also elicit fever. In contrast, one of its stereoisomers, N-acetylmuramyl-D-Ala-D-Glu-NH2, is devoid of both these activities. Our present report demonstrates that macromolecularization of muramyl dipeptide by attachment of several units to a multi-poly(DL-Ala)-poly(L-Lys) carrier potentiates both its pyrogenic and its immunostimulant activity. This branched polymer has been extensively used as carrier to various haptens. Surprisingly, inactive N-acetylmuramyl-D-Ala-D-Glu-NH2, after conjugation under the same conditions, becomes capable of increasing nonspecific immunity although its lack of pyrogenicity is not greatly modified. Moreover, the N-acetylmuramyl-D-Ala-D-Glu--NH2 conjugate remains devoid of adjuvant, sensitizing, or eliciting activity.
N-乙酰胞壁酰-L-丙氨酸-D-谷氨酸-NH2（胞壁酰二肽）及其几种衍生物是有效的免疫激活剂，它们既能增强对感染的非特异性抵抗力，也能引起发热。相比之下，其一种立体异构体N-乙酰胞壁酰-D-丙氨酸-D-谷氨酸-NH2则既无上述两种活性。我们目前的报告表明，通过将几个单元连接到多聚（DL-丙氨酸）-聚（L-赖氨酸）载体上使胞壁酰二肽大分子化，可增强其致热活性和免疫刺激活性。这种支链聚合物已被广泛用作各种半抗原的载体。令人惊讶的是，无活性的N-乙酰胞壁酰-D-丙氨酸-D-谷氨酸-NH2在相同条件下共轭后，虽然其无致热原性没有太大改变，但却能够增强非特异性免疫力。此外，N-乙酰胞壁酰-D-丙氨酸-D-谷氨酸-NH2共轭物仍然没有佐剂、致敏或激发活性。
