Immunoadjuvant activities of synthetic 6-O-acyl-N-acetylmuramyl-L-alanyl-D-isoglutamine with special reference to the effect of its administration with liposomes.

Addition of a lauroyl, stearoyl or docosanoyl group to the primary hydroxy group at the C-6 position of N-acetylmuramyl-L-alanyl-D-isoglutamine gave lipophilic derivatives that had definite adjuvancies in induction of delayed-type hypersensitivity and enhancement of antibody production against a test protein antigen, ovalbumin, when administered to guinea pigs as liposomes, that is without mineral oil. When administered as mineral oil-in-water emulsion, including Ribitype emulsions, rather than as water-in-mineral oil emulsions, N-acetylmuramyl-L-alanyl-D-isoglutamine and its 6-O-acyl derivatives showed only weak immunoadjuvancies.

Chemical studies on tuberactinomycin. XV. Total synthesis of tuberactinomycin O.

Tuberactinomycin O, one of the four congeners of the antituberculous peptide tuberactinomycin, was totally synthesized. The beta-ureidodehydroalanine moiety was constructed from beta,beta-diethoxyalanine with excess urea in acidic medium after a cyclization reaction of a pentapeptide was finished. Cyclization was carried out by means of the 1-succinimidyl ester method.

The revised structure of capreomycin.

The total structures of capreomycins IA and IB were determined mainly from the results of the comparative study on the NMR spectra of capreomycins and tuberactinomycins, resulting in a revision of the formerly proposed structure. The beta-lysine residue as a branched part was revealed to be linked with the beta-amino group of the alpha, beta-diaminopropionic acid residue in the cyclic pentapeptide moiety in a different manner than in tuberactinomycins.

The chemical structure of capreomycin.

The chemical structure of capreomycin, antituberculous peptide antibiotic, was revised from the results of NMR-analysis in comparison with tuberactinomycins. Capreomycin IA and IB were concluded to possess the similar amino acid sequences in their cyclic peptide moieties to those of tuberactinomycins.

Correlation between the immunoadjuvant activities and pyrogenicities of synthetic N-acetylmuramyl-peptides or -amino acids.

A total of 14 different N-acetylmuramyl-peptides or -amino acids with or without configurations inherent to bacterial cell wall peptidoglycans were synthesized and their pyrogenicities on intravenous injection into rabbits were tested. N-Acetylmuramyl-peptides, and especially N-acetylmuramyl-L-alanyl-D-isoglutamine and N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-lysine, which were previously shown to be adjuvant-active in both induction of delayed-type hypersensitivity and stimulation of increased serum antibody levels to ovalbumin in guinea pigs, exhibited distinct pyrogenicity at as low dose as 16 mug per rabbit. However, none of the adjuvant-inactive analogues or diastereomers of the above N-acetylmuramyl-dipeptide or related compounds caused any significant febrile response in rabbits, even at a dose of 250 mug per animal.

The total structure of the antibiotic longicatenamycin.

The peptide antibiotic longicatenamycin produced by a Streptomyces strain S-520 is a complex mixture of several congeners. The determination of the total structure of longicatenamycin was performed on the mixture using the procedure of N-bromosuccinimide oxidation followed by EDMAN degradation. The structure of the most abundant congener of longicatenamycin can be represented as cyclo (glycyl-L-2-amino-6-methylheptanoyl-D-valyl-D-ornithyl-threo-beta-hydroxy-L-glutamyl-5-chloro-D-tryptophyl) (Fig.

Chemical studies on tuberactinomycin. VIII. Isolation of tuberactinamine N, the cyclic peptide moiety of tuberactinomycin N, and conversion of tuberactinomycin N to O.

Tuberactinamine N, the cyclic peptide moiety of tuberactinomycin N, was obtained in a crystalline state through liberation of gamma-hydroxy-beta-lysine from tuberactinomycin N by acid treatment. Tuberactinamine N possesses an intramolecular hydrogen bond in its molecule and showed antibacterial activities comparable to those of the original antibiotics. Conversion of tuberactinomycin N to O was achieved through coupling of diacyl-beta-lysine with tuberactinamine N followed by removal of the protecting groups.