End-functionalized Poly Ethylene Glycol Research Articles

Polymer-Protein Hybrid Network Involving Mucin: A Mineralized Biomimetic Template for Bone Tissue Engineering.

Biomimetic matrices offer a great advantage to understand several biological processes including regeneration. The study involves the development of a hybrid biomimetic scaffold and the uniqueness lies in the use of mucin, as a constituent protein. Through this study, the role of the protein in bone regeneration is deciphered through its development as a 3D model. As a first step towards understanding the protein, the interactions of mucin and collagen are determined by in silico studies considering that collagen is the most abundant protein in the bone microenvironment. Both proteins are reported to be involved in bone biology though the exact role of mucin is a topic of investigation. The in silico studies of collagen-mucin suggest to have a proper affinity toward each other, forming a strong basis for 3D scaffold development. The developed 3D scaffold is a double network system comprising of mucin and collagen and vinyl end functionalized polyethylene glycol. In situ deposition of mineral crystals has been performed enzymatically. Biological evaluation of these mineral deposited scaffolds is done in terms of their bone regeneration potential and a comparison of the two systems with and without mineral deposition is presented.

An efficient synthesis of low-covered polyrotaxanes grafted with poly(ε-caprolactone) and the mechanical properties of its cross-linked elastomers

Advanced polyrotaxane elastomers were fabricated by the synthesis of poly(ε-caprolactone)-grafted polyrotaxanes with significantly lower coverage than previously achieved. The time course for the complexation of α-cyclodextrin with an end-functionalized polyethylene glycol (PEG) was analyzed by subsequent end-capping and polyrotaxane isolation, which revealed that the bulkiness of the PEG end group affects the time required for complex nucleation and the resulting coverage. Low-coverage poly(ε-caprolactone)-grafted polyrotaxanes were synthesized in a facile and large-scale manner by optimizing the simultaneous hydrolysis of the end-capping groups and the solubility of the product during the ring-opening polymerization of ε-caprolactone. Cross-linking the thermoplastic graft polyrotaxanes yielded elastomers that are much more extensible than conventional elastomers with fivefold higher coverages. Elastomers with lower coverages behave as ideal elastic bodies due to chain sliding through the cross-links, which suggests that the arrangement entropy of the cyclic components, which counteracts chain sliding, is substantially decreased by reduced coverage.

Synthesis of graft polyrotaxane by simultaneous capping of backbone and grafting from rings of pseudo-polyrotaxane.

Graft polyrotaxanes, with poly(ε-caprolactone) (PCL) graft chains on the ring components were synthesized by the simultaneous ring-opening polymerization of ε-caprolactone from both ends of the backbone polymer, an end-functionalized polyethylene glycol (PEG) and the formation of inclusion complexes with α-cyclodextrin (α-CD). PEG with multiple functional groups at each end was prepared by the condensation of PEG-amine and D-gluconic acid; the PEG derivative formed an inclusion complex with α-CD. The polymerization of multiple hydroxy groups at the backbone ends resulted in a star-shaped end group, which served as a bulky capping group to prevent dethreading. In contrast, PEG with only one hydroxy group at each end did not produce polyrotaxanes, indicating that single PCL chains were too thin to confine α-CDs to the complex. In addition, the grafting polymerization proceeded properly only when robust hydrogen bonds formed between α-CDs were dissociated using a basic catalyst. Since the dissociation also induced dethreading, kinetic control of the polymerization and dissociation were crucial for producing graft polyrotaxanes. Consequently, this three-step reaction yielded graft polyrotaxanes in a good yield, demonstrating a significant simplification of the synthesis of graft polyrotaxanes.

Facile in situ PEGylation of polyamide thin film composite membranes for improving fouling resistance

We report a novel approach for in situ PEGylation of thin film composite (TFC) reverse osmosis (RO) membrane for sustained performance. The approach was based on use of end-functionalized polyethylene glycol (MPD-PEG-MPD or MeO-PEG-MPD) with end groups structure resembling the structure of m-phenylenediamine (MPD), commonly used for preparation of TFC membrane. Michael addition reaction between MPD and acrylate-terminated-polyethylene glycol (AA-PEG-AA or MeO-PEG-AA) produces such type of end-functionality for further use in interfacial polymerization (IFP) with conventionally used trimesoyl chloride (TMC). PEGylated TFC membranes exhibited superior antifouling property during water desalination in presence of fouling agent (protein) compared to non-PEGylated TFC membrane. The best results were obtained with the membranes prepared by addition of 0.25–0.5% (w/v) of AA-PEG-AA or MeO-PEG-AA to the MPD solution (2% w/v in water) for Michael addition reaction prior to IFP with TMC (0.125% w/v in hexane) in as much as the antifouling property was enhanced and the performance (salt rejection efficiency and flux) remained almost unaffected. TFC membranes were characterized by Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), contact angle (θ), scanning electron microscope (SEM), atomic force microscope (AFM) and CHN analyses. The incorporated PEG remained stable in the polyamide network and is mainly attributed to the participation of both MPD and MPD-PEG-MPD or MeO-PEG-MPD in the IFP process.

Improved bioavailability of inhibitors of Trypanosoma cruzi trans-sialidase: PEGylation of lactose analogs with multiarm polyethyleneglycol

The trans-sialidase of Trypanosoma cruzi (TcTS) catalyzes the transfer of sialic acid from host glycoconjugates to terminal β-galactopyranosides in the mucins of the parasite. During infection, the enzyme is actively shed by the parasite to the bloodstream inducing hematological alterations. Lactitol prevents cell apoptosis caused by the TcTS, although it is rapidly eliminated from the circulatory system. Linear polyethyleneglycol (PEG) conjugates of lactose analogs were prepared but their clearance from blood was still quite fast. With the aim of improving their circulating half-lives in vivo, we now synthesized covalent conjugates of eight-arm PEG. The star-shape of these conjugates allows an increase in the molecular weight together with the loading of the active sugar. Two approaches were used for PEGylation of disaccharide derivatives containing β-D-Galp as the non-reducing unit. (1) Amide formation between benzyl β-D-galactopyranosyl-(1→6)-2-amino-2-deoxy-α-D-glucopyranoside and a succinimide-activated PEG. (2) Conjugation of lactobionolactone with amino end-functionalized PEG. Two 8-arm PEG derivatives (20 and 40 kDa) were used for each sugar. Substitution of all arms was proved by (1)H nuclear magnetic resonance (NMR) spectroscopy. The bioavailability of the conjugates in mice plasma was considerably improved with respect to the 5 kDa linear PEG conjugates retaining their inhibitory properties.

Combining Modular Ligation and Supramolecular Self‐Assembly for the Construction of Star‐Shaped Macromolecules

A well-defined random copolymer of styrene (S) and chloromethylstyrene (CMS) featuring lateral chlorine moieties with an alkyne terminal group is prepared (P(S-co-CMS), M(n) = 5500 Da, PDI = 1.13). The chloromethyl groups are converted into Hamilton wedge (HW) entities (P(S-co-HWS), M(n) = 6200 Da, PDI = 1.13). The P(S-co-HWS) polymer is subsequently ligated with tetrakis(4-azidophenyl)methane to give HW-functional star-shaped macromolecules (P(S-co-HWS))(4), M(n) = 25,100 Da, PDI = 1.08). Supramolecular star-shaped copolymers are then prepared via self-assembly between the HW-functionalized four-arm star-shaped macromolecules (P(S-co-HW))(4) and cyanuric acid (CA) end-functionalized PS (PS-CA, M(n) = 3700 Da, PDI = 1.04), CA end-functionalized poly(methyl methacrylate) (PMMA-CA, M(n) = 8500 Da, PDI = 1.13) and CA end-functionalized polyethylene glycol (PEG-CA, M(n) = 1700 Da, PDI = 1.05). The self-assembly is monitored by (1)H NMR spectroscopy and light scattering analyses.

Hydrophobic Forces, Electrostatic Steering, and Acid–Base Bridging between Atomically Smooth Self-Assembled Monolayers and End-Functionalized PEGolated Lipid Bilayers

A molecular level understanding of interaction forces and dynamics between asymmetric apposing surfaces (including end-functionalized polymers) in water plays a key role in the utilization of molecular structures for smart and functional surfaces in biological, medical, and materials applications. To quantify interaction forces and binding dynamics between asymmetric apposing surfaces in terms of their chemical structure and molecular design we developed a novel surface forces apparatus experiment, using self-assembled monolayers (SAMs) on atomically smooth gold substrates. Varying the SAM head group functionality allowed us to quantitatively identify, rationalize, and therefore control which interaction forces dominated between the SAM surfaces and a surface coated with short-chain, amine end-functionalized polyethylene glycol (PEG) polymers extending from a lipid bilayer. Three different SAM-terminations were chosen for this study: (a) carboxylic acid, (b) alcohol, and (c) methyl head group terminations. These three functionalities allowed for the quantification of (a) specific acid-base bindings, (b) steric effects of PEG chains, and (c) adhesion of hydrophobic segments of the polymer backbone, all as a function of the solution pH. The pH-dependent acid-base binding appears to be a specific and charge mediated hydrogen bonding interaction between oppositely charged carboxylic acid and amine functionalities, at pH values above the acid pK(A) and below the amine pK(A). The long-range electrostatic "steering" of acid and base pairs leads to remarkably rapid binding formation and high binding probability of this specific binding even at distances close to full extension of the PEG tethers, a result which has potentially important implications for protein folding processes and enzymatic catalysis.

Modulating Biofunctional starPEG Heparin Hydrogels by Varying Size and Ratio of the Constituents

Heparin and four-armed, end-functionalized polyethylene glycol (starPEG) were recently combined in sets of covalently linked biohybrid hydrogel networks capable of directing various therapeutically relevant cell types. To extend the variability and applicability of this novel biomaterials platform, the influence of size and molar ratio of the two building blocks on the hydrogel properties was investigated in the present study. Heparin and starPEG were converted in various molar ratios and in different molecular weights to tune swelling, stiffness and pore size of the obtained polymer networks. Hydrogels with a range of elastic moduli could be generated by controlling either the crosslinking density or the chain length of the starPEG, whereas altering the molecular mass of heparin did not significantly affect hydrogel strength. The concentration of heparin in the swollen gels was found to be nearly invariant at varying crosslinking degrees for any given set of building blocks but adjustable by the size of the building blocks. Since heparin is the base for all biofunctionalization schemes of the gels these findings lay the ground for an even more versatile customization of this powerful new class of biomaterials.