Enhancement of Certain Biological Activities of Muramyl Dipeptide Derivatives after Conjugation to a Multi-poly(DL-alanine)--poly(L-lysine) Carrier

N-Acetylmuramyl-L-Ala-D-Glu-NH$_{2}$ (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-NH$_{2}$, 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-NH$_{2}$, 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-NH$_{2}$ conjugate remains devoid of adjuvant, sensitizing, or eliciting activity.