The Effect of PEGylation on Multivalent Binding: A Surface Plasmon Resonance and Isothermal Titration Calorimetry Study with Structurally Diverse PEG‐Dendritic GATG Copolymers

Abstract

Ag eneral synthetic strategy to polyethylene glycol (PEG)-dendritic block copolymers of the GATG (gallic acid-triethylene glycol)f amilyi sd escribed from commercially availableP EG of different molecular weights and architectures. Glycosylationo ft he resulting azide-terminated copolymers with fucose by copper-catalyzed azide-alkyne cycloaddition (CuAAC)a fforded at oolbox to study the effect of PEG on the multivalent binding with the lectin UEA-I by surface plasmon resonance (SPR, on surface) and isothermal titration calorimetry (ITC, in solution). Our resultsi ndicatet hat PEG reducest he affinity of glycodendrimers towards lectins by steric hindrance in am olecular-weight-dependent fashion. Great differences were observeda saf unctiono ft he PEG architecture, with diblock PEG-dendritic copolymers benefiting from ap ositive entropic contribution (PEG folding), not seen in the dendritic-PEG-dendritic systems. Thes elf-inflicted steric stabilization of the PEGylated copolymers onto lectin clustersr eveals the necessity of additional competitive experiments to fully assess the antiadhesive properties of PEG in biological environments.

A dendrimer–hydrophobic interaction synergy improves the stability of polyion complex micelles

“…The synthesis of the PEG-GATG block copolymers is depicted in Figure 2 and described in detail in the Electronic Supplementary Information (ESI). In brief, three G of PEG-GATG block copolymers carrying terminal azides (PEG-[Gn]-N 3 ; n = 2, 3, 4) and PEG chains of different lengths 28,37 were peripherally decorated at the dendritic block with alkynated anionic residues 1 and 2 via triazol linkers generated by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). 20,38 Preliminary experiments on the formation of PIC micelles were performed in 10 mM PB, pH 7.4 with PLL 108 and PEG 5000 -[G3]-CO 2 -, 20 a dendritic block copolymer displaying 27 carboxylate groups (Figure 2).…”

Self-assembled Dendritic Boronate Micelles as a Promising Delivery Strategy for Gemcitabine

“…A linear-dendritic block copolymer PEG-[G3]-N 3 previously described by our group, 35 which incorporates a PEG chain of 5 kDa and a dendritic block of third generation (G3) with 27 peripheral azide groups, was selected for the functionalization with boronic acids. To this end, a one-pot, three-step protocol was implemented, comprising an initial Staudinger reduction of the terminal azides to primary amines with PPh3, followed by reductive amination with 2-formylphenylboronic in the presence of NaBH4.…”

“…31,32,33,34 They are composed of a repeating unit incorporating a gallic acid core and hydrophilic triethylene glycol arms carrying terminal azides. When combined with PEG following a divergent strategy, the resulting PEG-GATG copolymers 35 have been exploited in a plethora of drug delivery and diagnosis applications. 36,37,38 Boronic acids have recently emerged as an appealing functional group with a high stability and low toxicity profile.…”

Interactive Polymer Gels as Biomimetic Sensors for Carbohydrate Interactions and Capture–Release Devices for Pathogens

“…[3,47] However, additional molecular-scale details of the multivalent binding modes besides the statistical effects could not be seen via SCP adhesion. Other direct binding assays using various scaffolds such as dendrimers [48] or nanoparticles [49] as scaffolds also mainly showed additive effects due to the multivalent presentation of carbohydrates, but not positively cooperative interactions due to chelate-like binding or subsite binding to the receptor. To shed more light on the molecular mechanisms of carbohydrate binding X-ray crystallography, [50][51][52][53] or single molecule techniques based on labeled carbohydrates for NMR spectroscopy [54] and single molecule AFM [55][56][57][58][59][60] were used.…”