The experimental system utilized in investigating the correlation between the chemical structures of muramyl
peptides and their protective activities in the
sepsis type of systemic
infections caused by Escherichia coli was applied in evaluating the enhancement of resistance to
infection induced by 32 synthetic
glycopeptide analogs, including 6-O-acyl derivatives and 1-alpha-O-benzyl derivatives of
muramyl dipeptide (N-acetyl muramyl-L-alanyl-D-
isoglutamine). In assessing the 6-O-acyl derivatives of
muramyl dipeptide, we found that the degree of protective activity was attributable to the kinds of
fatty acids introduced. Acylation of the 6-hydroxy group on the
muramic acid moiety in
muramyl dipeptide with natural
mycolic acid or a synthetic
fatty acid possessing either an alpha-branched or an alpha-branched, beta-hydroxylated group resulted in a decrease in or a disappearance of the protective activity of
muramyl dipeptide. Acylation with a normal
fatty acid or an iso
fatty acid resulted in a retention or enhancement of
muramyl dipeptide activity. The activity of acylated derivatives containing linear
fatty acids was stimulated by increasing the chain length up to 18
carbon atoms. The highest degree of protective activity occurred with the derivatives acylated with straight-chain
fatty acids, particularly with the derivatives acylated with
palmitic acid and
arachidic acid. Benzylation of the 1-hydroxy group of
muramyl dipeptide resulted in a decrease in or a loss of protective activity.