Enhancement of certain biological activities of muramyl dipeptide derivatives after conjugation to a multi-poly (DL-alanine)--poly (L-lysine) carrier.

L Chedid, M Parant, F Parant… - Proceedings of the …, 1979 - National Acad Sciences
L Chedid, M Parant, F Parant, F Audibert, F Lefrancier, J Choay, M Sela
Proceedings of the National Academy of Sciences, 1979National Acad Sciences
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 …
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.
National Acad Sciences