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

Abstract
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. One of its stereosisomers, N-acetylmuramyl-D-Ala-D-Glu-NH2, is devoid of both these activities. In this study macromolecularization of muramyl dipeptide by attachment of several units to a multi-poly(DL-Ala)--poly(L-Lys) carrier potentiated its pyrogenic and its immunostimulant activity [in rabbits and guinea pigs]. This branched polymer has been extensively used as carrier to various haptens. 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. The N-acetylmuramyl-D-Ala-D-Glu-NH2 conjugate remains devoid of adjuvant, sensitizing or eliciting activity.

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