Facile synthesis of pH‐responsive glycopolypeptides with adjustable sugar density

Abstract

Well‐defined pH‐responsive glycopolypeptides were prepared by polymer‐analogous aqueous amide coupling of d‐glucosamine to poly(α,l‐glutamic acid) (PGA) using the coupling agent 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium chloride (DMT‐MM) without any organic solvents, additives, or buffers. Degrees of substitution (DS) up to 80% can be achieved, and the DS is adjustable by the molar ratio of DMT‐MM to PGA repeating units. Successful glycosylation of both low MW and high MW PGA was confirmed by 1H NMR and FTIR spectroscopy as well as by an enhanced solubility at low pH. CD spectroscopy revealed that glycosylated PGAs with a DS up to 0.63 are able to undergo a pH‐responsive and reversible helix‐coil transition. However, for polymers with higher DS no transition occurs. A comparison with PGAs functionalized with monoethanolamine showed that the low helicity at high DS is not a steric effect due to the bulky sugar moieties, but a solvation effect. Preliminary turbidimetric tests with the lectin Concanavalin A indicate a biological activity of these glycosylated polypeptides. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3925–3931

Thermoresponsive glycopolypeptides with temperature controlled selective lectin binding properties

“…With the addition of more galactose the helicity increases to 55.6%. This is in contrast to the recently reported decrease of helicity with increasing degree of amino sugars directly attached to poly(glutamic acid) [30,39]. Without a further systematic study it can only be speculated that this is due to the different side chain structures of both systems.…”

“…As a result, polypeptides promise potential in biomedical fields such as drug delivery [16][17][18][19][20][21], tissue engineering [22] or imaging [23]. The synthesis of glycosylated polypeptides has been achieved using direct polymerization of glycosylated NCA or post-modification by conventional chemistry as well as click chemistry [24][25][26][27][28][29][30][31]. On the other hand, a range of thermoresponsive polypeptides have been described in the literature [21,[32][33][34][35].…”

Facile Synthesis of Fluorescent Latex Nanoparticles with Selective Binding Properties Using Amphiphilic Glycosylated Polypeptide Surfactants

“…A procedure described by Menzel 43 was employed to attach D-galactosamine (GA) to the carboxylic acid moieties of the PS 45 -b-PLGA 66 to prepare PS 45 -b-(PLGA 31 -r-GA 35 ) 66 (5) (Figure S4). 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) is a mild and efficient amide-coupling agent, which was used to facilitate the reaction.…”

“…Glycosylation of the carboxylic acid moieties was achieved according to a modified literature procedure. 43 PS 45 -b-PLGA 66 (0.75 g, 5.7 × 10 −5 mol) and galactosamine hydrochloride (0.43 g, 2.0 mmol, 33 equiv with respect to repeating units) were dissolved in deionized water (12 mL) and stirred for 15 min. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) (0.55 g, 2.0 mmol, 1 equiv to galactosamine HCl) was dissolved in 5 mL of deionized water and added to the reaction mixture.…”

Recent advances in glycopolypeptide synthesis

“…86 A different approach to prepare amide-linked glycopolypeptides was taken recently by Menzel, who used poly(L-glutamic acid), poly(L-Glu), as the polypeptide precursor and formed glycopolypeptides by reactions with amino sugars. 87 The coupling reactions were promoted using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), which is a mild and very efficient amide coupling agent compatible with the reagents used. Conjugation of glucosamine units to the polypeptide was found to be highly efficient (90%) at low loading ratios (less than 40% amino sugar per carboxylate), but decreased at higher sugar loadings, with the maximum loading of sugars being approximately 80%.…”