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-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.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000367:Age Factors; D001424:Bacterial Infections / Q000276:immunology / Q000517:prevention & control; D002352:Carrier Proteins / Q000276:immunology*; D006020:Glycopeptides / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007710:Klebsiella Infections / Q000276:immunology / Q000517:prevention & control; D011749:Pyrogens; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; D006020:Glycopeptides; D011749:Pyrogens; D000119:Acetylmuramyl-Alanyl-Isoglutamine