Synthesis and Immunomodulating Activity of New Glycopeptides of Glycyrrhizic Acid Containing Residues of L-Glutamic Acid

R. M. Kondratenko¹, L. A. Baltina Jr.², L. A. Baltina^2 #, N. Zh. Baschenko², and G. A. Tolstikov³

^#Phone: (3472) 35-52-88; e-mail: baltina@anrb.ru
¹Bashkortostan State Medical University, Ufa, Bashkortostan, Russia
²Bashkir Research Center, Institute of Organic Chemistry, pr. Oktyabrya 71, Ufa, 450054, Bashkortostan, Russia
³Vorozhtsov Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, Novosibirsk, Russia
Received: December 26, 2005;  in final form: April 6, 2006

Abstract: New glycopeptides of glycyrrhizic acid (GA) containing Glu residues and their α-methyl esters, γ-methyl esters, and α,γ-dimethyl esters were synthesized using N,N′-dicyclohexylcarbodiimide in the presence of N-hydroxybenzotriazole or N-hydroxysuccinimide. Formation of amide bonds was observed on all the three COOH groups of GA, or selectively on the COOH groups of the GA carbohydrate part in dependence on the ratio of reagents and the reaction conditions. The GA glycopeptide with three residues of Glu(OH)-OMe at a dose of 2 mg/kg stimulated the production of antibody-forming cells in mouse spleen in comparison with the control. The GA glycopeptide containing Glu residues only in the GA carbohydrate part turned out to be an immunosuppressor. The glycopeptide of the 30-methyl ester of GA with residues of free Glu in its carbohydrate part increased the hemagglutinine titer at oral doses of 2 and 10 mg/kg. All the studied compounds had practically no effect on the delayed-type hypersensitivity in mice.

Key words: glutamic acid, glycopeptides, glycyrrhizic acid, immunomodulating activity

Russian Journal of Bioorganic Chemistry 2006, 32 (6): 595-601