A shortened synthesis of adjuvant dipeptide (MDP).
N-acetylmuramyl-L-alanyl-D-isoglutamine, or muramyl dipeptide (MDP), has been shown to be the minimal structure necessary for adjuvant activity. This compound can replace whole mycobacteria in Freund's complete adjuvant. In our continuing investigation of bacterial cell wall fragments of biological and immunotherapeutic interest, the necessity of obtaining MDP analogs of varying structure has proven to be of primary importance. We have found that the published routes to MDP could be effectively shortened to four steps starting from commercially available starting materials. As an example of this scheme, synthesis of the seryl analog will be detailed. gamma-benzyl glutamic acid could be elaborated in one step to the N-tertiary butoxycarbonyl seryl-gamma-benzyl isoglutamine. Deprotection of the Boc group followed by condensation with 1-O-benzyl-4, 6-O-benzylidine N-acetyl muramic acid provided the protected MDP. Deprotection of this product by hydrogenolysis gave the final product. Physical chemical and biological data as proof of structure is presented. Utility of these compounds in the line-10 tumor system is demonstrated.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D000276:Adjuvants, Immunologic; D000818:Animals; D002642:Chick Embryo; D003311:Cord Factors / Q000627:therapeutic use; D006020:Glycopeptides / Q000138:chemical synthesis*; D006168:Guinea Pigs; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy; D011487:Protein Conformation; D011817:Rabbits; D013057:Spectrum Analysis
D000276:Adjuvants, Immunologic; D003311:Cord Factors; D006020:Glycopeptides; D000119:Acetylmuramyl-Alanyl-Isoglutamine