Synthesis and immunomodulator activity of glycan-based polyelectrolytes

Abstract

As is known, some water-soluble polyelectrolytes (glycans, nucleic acids, synthetic polycarboxylic acids and their copolymers with pyridine derivatives, etc.) exhibit adjuvant properties when introduced into the organism together with antigens [1]. However, most of the synthetic polyelectrolytes exhibit increased toxicity, which is an obstacle for their use in immunolo~cal research [2]. A promising way to the creation of low-toxicity polymers possessing immunomodulator properties consists in the chemical modification of glycans that are characterized by detoxicating effect and are capable of prolonging and au.~aenting the action of drugs used for chemotherapy. Smirnova et al. [3] reported on the synthesis of an oxyglycan based on mannan, a microbial poIysaccharide capable of stimulating the immune response [3].The purpose of this work was to synthesize nontoxic water-soluble polymers (analogs of oxystarch and inulin), containing amino acid and hydroxyalkyl(alkyl)amino groups and study their biolo~cal activity.The oxystarch was obtained through the oxidation of starch by the persulfate method, whereby 12% aldehyde and 8% carboxy groups (occupying predominantly the C o and C 3 positions) are formed in the structure [4].The starch-based cation-active derivatives were synthesized by interaction of oxyglycan with (3-chloro-2-hydroxypropyl)tri(2-hydroxyethyl)ammonium chloride or triethylamine with the formation of ethers and salts (I and II, respectively). The carionization of inulin was performed by, its interaction with di(2-hydroxyethyl)amine and formaldehyde (the Marmieh reaction). The resulting amino-containing ethers are probably substituted at the C 6 site (V). The results of periodate oxidation indicate that OH groups in positions C 3 and C 4 (a-glycol group) are free (as is known, some structtaaI features of inulin hinder substitution of these hydroxy groups) [5,6]. 80,c3/H~H OH Starch analogs of the ampholytic type were obtained by the reaction of oxystarch with N-0aydroxymethyl)-L-gluramie acid (leading to the formation of iminium-salt structural elements with an aldehyde group conversion from 3 to 12%, IVa-IVc) and lysine (with the formation of azomethine group, liD. Compounds I-V were synthesized in an aqueous medium at a temperature of 50-70~ The structures of polymer analogs were confirmed by IR spectroscopic data and the results of elemental analyses. EXPERIMENTAL CHEMICAL PARTThe IR spectra of synthesized compounds were measured on an IKS-29 spectrophotomcter.Compounds I -V were purified by ultrafiltmtion through fluoroplastic membranes with a pore diameter of 50 A for compound V and 200 A for compounds I -IV.