Chemical Modification of Chitosan. 3. Hyperbranched Chitosan−Sialic Acid Dendrimer Hybrid with Tetraethylene Glycol Spacer

Abstract

Chitosan is a polysaccharide composed mainly of β-(1-4)-2-amino-2-deoxy-D-glucopyranose repeating units. Chitosan shows interesting biological properties such as immunological, 1 antibacterial, 2,3 and wound healing activity. 4 Moreover, it is a nontoxic 3 and biodegradable polymer, 5 and the free amino groups of chitosan offer great potential for further derivatization. Alternatively, dendrimers also offer several possibilities in molecular design owing to their multifunctional attachment sites. They have been used to scaffold neoglycoconjugates, 6 probes, catalysts, and so on. 7 Herein we report the preparation of sialic acid bound dendronized 8 chitosandendrimer hybrids. These molecules may have the potential to inhibit the hemagglutination of human erythrocytes by influenza virus hemagglutinin as recently observed with straight polymers and hyperbranched polymers. 6 As polymer backbones used so far are highly toxic, it is expected that scaffolding poly-(amidoamine) (PAMAM) dendrimer onto nontoxic chitosan core would present biopharmaceutical advantage.To build up the desired long spacer necessary to allow multiple branch construction, commercial tetraethylene glycol 1 was modified into aminoacetal 6 in five steps (Scheme 1). Monotosylate 2 was prepared from 1 in only 40% yield (TsCl, 1.0 equiv, Et 3 N, CH 2 Cl 2 ) owing to the simultaneous formation of undesired ditosylate. According to a published procedure, 9,10 oxidation (DMSO, P 2 O 5 , CH 2 Cl 2 ) and acetal formation (HOCH 2 CH 2 OH, pTsOH, PhH) were performed in good yields (3, 92%; 4, 89%). After azide displacement and reduction [(i) NaN 3 , EtOH; (ii) H 2 , 10% Pd-C, EtOH], 11 amine 6 was obtained in 23% overall yield from 1. Using 6 as an amine source, poly(amidoamine) (PAMAM) dendrimers were prepared according to Tomalia et al. 12 by repeating cycle of methyl acrylate and ethylenediamine treatment. The methyl esters of each dendrimers 7a-c (G ) 0.5, 1.5, 2.5) were purified by silica gel column chromatography (CH 2 Cl 2 / MeOH ) 10/1) which were obtained in moderate to good yields (7a, G ) 0.5, 70%; 7b, G ) 1.5, 73%; 7c, G ) 2.5, 57%). The terminal amines of each generation (G ) 1, G ) 2, and G ) 3, 8a-c) were obtained from each methyl esters quantitatively by treatment with excess ethylenediamine at room temperature for 3 days.The sialic acid residues were initially attached onto each dendrimer by reductive N-alkylation with known p-formylphenyl R-sialoside 9 13 using NaCNBH 3 in methanol (Scheme 2). 14 Since 3 equiv of aldehyde 9 was used

Layer‐by‐Layer Buildup of Poly(L‐glutamic acid)/Chitosan Film for Biologically Active Coating

“…CS and PGA were chosen not only because they are biocompatible, but also because they offer the possibility of being easily conjugated with bioactive molecules. [33][34][35][36] The electrostatic assembly was confirmed by FT-IR measurements, and the adsorption process was monitored stepwise using UV-vis spectroscopy and a dissipation-enhanced quartz crystal microbalance (QCM-D). Because of the unique properties of CS and PGA, multilayer films composed of these substances are expected to be interesting for cell growth, such as muscle myoblast cells (C2C12).…”

Preparation of low molecular weight N-maleated chitosan-graft-PAMAM copolymer for enhanced DNA complexation

“…Thereafter, full generation PAMAM dendrimers (G1-G3) were grafted onto chitosan through N-maleated chitosan by Michael type addition reaction. In comparison to the graft copolymer of Sashiwa et al [24,25], the graft copolymer reported in this paper is unique with respect to mode of preparation and properties. All the related properties such as its solubility, complexation with DNA, in vitro cytotoxicity and in vitro DNA release study were investigated in details in this paper.…”

“…Therefore, the chemical combination of chitosan with PAMAM dendrimers may provide novel biomaterial with improved water solubility, higher charge density and lower toxicity. Sashiwa et al [24,25] prepared chitosan-graft-PAMAM copolymers through tetraethylene glycol spacer by reductive Nalkylation, but till date, no report is available about N-maleated chitosan-graft-PAMAM copolymer.…”

New-generation biomedical materials: Peptide dendrimers and their application in biomedicine

“…Various classes of these compounds differing in composition and structures were reported, together with their practical use extending from targeting drug delivery, catalysis, and transport vehicles to synthetic vaccines. The main stress was given to glycopeptide dendrimers, namely multiple antigen glycopeptides (MAGs) [55][56][57][58]. An example of glycopeptide dendrimer synthesis, where lactose ligands were introduced to the surface of lysine-based dendrimer, was reported by Uryu et al ( Figure 11) [59].…”