52 research outputs found
"Functional Poly(ethylene glycol)": PEG-Based Random Copolymers with 1,2-Diol Side Chains and Terminal Amino Functionality
A series of poly(ethylene glycol-co-isopropylidene glyceryl glycidyl ether) (P(EO-co-IGG)) random copolymers with different fractions of 1,2-isopropylidene glyceryl glycidyl ether (IGG) units was synthesized. After acidic hydrolysis a new type of "functional PEGs", namely poly(ethylene glycol-co-glyceryl glycerol) (P(EO-co-GG)) was obtained. Using an initiator that releases a terminal amino moiety after deprotection, functional end groups with orthogonal reactivity to the in-chain groups were obtained. All polymers showed narrow molecular weight distributions (1.07-1.19), and control of the molecular weights was achieved in the range 5000-30 000 g/mol. Random incorporation of both comonomers was verified by monitoring the copolymerization kinetics via real-time H-1 NMR spectroscopy during the polymerization and by characterization of the triad sequence distribution, relying on C-13 NMR analysis. Using the 1,2-diol component of the side chains allows for attachment and facile acid-catalyzed release of molecules bearing ketone/aldehyde functionalities. This renders the materials potentially useful as support for reagents, drugs or catalysts. This was demonstrated using benzaldehyde as a model compound. DSC was carried out on all samples, showing amorphous structures upon incorporation of IGG fractions exceeding 15%
From an Epoxide Monomer Toolkit to Functional PEG Copolymers With Adjustable LCST Behavior
The lower critical solution temperature (LCST) behavior of novel poly(ethylene glycol) (PEG)-based copolymers bearing multiple functional groups, obtained by anionic ring-opening (co)polymerization (AROP), has been investigated. Variable comonomer ratios of ethylene oxide (EO) and the corresponding oxiranes isopropylidene glyceryl glycidyl ether (IGG), ethoxyl vinyl glycidyl ether (EVGE), allyl glycidyl ether (AGE), or N,N-dibenzyl amino glycidyl (DBAG), particularly designed to implement functional groups at the PEG backbone, were found to influence the LCST behavior. Sharp transitions from translucent to opaque solutions, comparable to other well-established stimuli-responsive polymers, were observed at temperatures ranging from 9 to 82 degrees C. The influence of the side group hydrophobicity could be quantified by the comparison of the different copolymer systems observed
Squaric Acid Mediated Synthesis and Biological Activity of a Library of Linear and Hyperbranched Poly(Glycerol)-Protein Conjugates
Polymer-protein conjugates generated from side chain functional synthetic polymers are attractive because they can be easily further modified with, for example, labeling groups or targeting ligands. The residue specific modification of proteins with side chain functional synthetic polymers using the traditional coupling strategies may be compromised due to the nonorthogonality of the side-chain and chain-end functional groups of the synthetic polymer, which may lead to side reactions. This study explores the feasibility of the squaric acid diethyl ester mediated coupling as an amine selective, hydroxyl tolerant, and hydrolysis insensitive route for the preparation of side-chain functional, hydroxyl-containing, polymer-protein conjugates. The hydroxyl side chain functional polymers selected for this study are a library of amine end-functional, linear, midfunctional, hyperbranched, and linear-block-hyperbranched polyglycerol (PG) copolymers. These synthetic polymers have been used to prepare a diverse library of BSA and lysozyme polymer conjugates. In addition to exploring the scope and limitations of the squaric acid diethylester-mediated coupling strategy, the use of the library of polyglycerol copolymers also allows to systematically study the influence of molecular weight and architecture of the synthetic polymer on the biological activity of the protein. Comparison of the activity of PG-lysozyme conjugates generated from relatively low molecular weight PG copolymers did not reveal any obvious structure-activity relationships. Evaluation of the activity of conjugates composed of, PG copolymers with molecular weights of 10000 or 20000 g/mol, however, indicated significantly higher activities of conjugates prepared from midfunctional synthetic polymers as compared to linear polymers of similar molecular weight
PEG-based Multifunctional Polyethers with Highly Reactive Vinyl-Ether Side Chains for Click-Type Functionalization
Introduction of highly reactive vinyl ether moieties along a poly(ethylene-glycol) (PEG) backbone has been realized by copolymerization of the novel epoxide monomer ethoxy vinyl glycidyl ether (EVGE) with ethylene oxide (EO). A series of copolymers with varying structure (block and random) as well as EVGE comonomer content (5-100%) with molecular weights in the range of 3,900-13,200 g/mol and narrow molecular weight distributions (M-w/M-n = 1.06-1.20) has been synthesized and characterized with respect to their microstructure and thermal properties. The facile transformation of the vinyl ether side chains in click type reactions was verified by two different post polymerization modification reactions: (i) thiol-ene addition and (ii) acetal formation, employing various model compounds. Both strategies are very efficient, resulting in quantitative conversion. The rapid and complete acetal formation with alcohols results in an acid-labile bond and is thus highly interesting with respect to biomedical applications that require slow or controlled release of a drug, while the thiol-ene addition to a vinyl ether prevents cross-linking efficiently compared to other double bonds
Squaric Acid Mediated Chemoselective PEGylation of Proteins: Reactivity of Single-Step-Activated alpha-Amino Poly(ethylene glycol)s
The covalent attachment of poly(ethylene glycol) (PEG) to therapeutically active proteins (PEGylation) has become an important method to deal with the pharmacological difficulties of these polypeptides, such as short body-residence times and immunogenicity. However, the derivatives of PEG used for PEGylation lack further functional groups that would allow the addition of targeting or labeling moieties. Squaric acid diethyl ester was used for the chemoselective single-step activation of poly(ethylene glycol)s into the respective ester amides. The resultant selective protein-reactive poly(ethylene glycol)s were investigated with respect to their selectivity towards amino acid residues in bovine serum albumin (as a model protein). The presented procedure relies on a robust two-step protocol and was found to be selective towards lysine residues; the activated polyethers are efficient and stoichiometric PEGylation agents with a remarkable hydrolytic stability over a period of several days. By adjusting the pD value of the conjugation mixture, the chemoselectivity of the activated PEGs towards the a- and e-amino groups of lysine methyl ester was effectively changed
Acid-Labile Surfactants Based on Poly(ethylene glycol), Carbon Dioxide and Propylene Oxide: Miniemulsion Polymerization and Degradation Studies
Squaric Acid Mediated Synthesis and Biological Activity of a Library of Linear and Hyperbranched Poly(Glycerol)–Protein Conjugates
Polymer–protein conjugates generated from side
chain functional
synthetic polymers are attractive because they can be easily further
modified with, for example, labeling groups or targeting ligands.
The residue specific modification of proteins with side chain functional
synthetic polymers using the traditional coupling strategies may be
compromised due to the nonorthogonality of the side-chain and chain-end
functional groups of the synthetic polymer, which may lead to side
reactions. This study explores the feasibility of the squaric acid
diethyl ester mediated coupling as an amine selective, hydroxyl tolerant,
and hydrolysis insensitive route for the preparation of side-chain
functional, hydroxyl-containing, polymer–protein conjugates.
The hydroxyl side chain functional polymers selected for this study
are a library of amine end-functional, linear, midfunctional, hyperbranched,
and linear-block-hyperbranched polyglycerol (PG) copolymers. These
synthetic polymers have been used to prepare a diverse library of
BSA and lysozyme polymer conjugates. In addition to exploring the
scope and limitations of the squaric acid diethylester-mediated coupling
strategy, the use of the library of polyglycerol copolymers also allows
to systematically study the influence of molecular weight and architecture
of the synthetic polymer on the biological activity of the protein.
Comparison of the activity of PG–lysozyme conjugates generated
from relatively low molecular weight PG copolymers did not reveal
any obvious structure–activity relationships. Evaluation of
the activity of conjugates composed of PG copolymers with molecular
weights of 10000 or 20000 g/mol, however, indicated significantly
higher activities of conjugates prepared from midfunctional synthetic
polymers as compared to linear polymers of similar molecular weight
Hyperbranched polyglycerol-based lipids via oxyanionic polymerization : toward multifunctional stealth liposomes
We describe the synthesis of linear-hyperbranched lipids for liposome preparation based on linear poly(ethylene glycol) (PEG) and hyperbranched polyglycerol (PG). Molecular weights were adjusted 10 values around 3000 g/mol with varying degrees of polymerization of the linear and the branched segments in analogy to PEG-based stealth lipids; polydispersities were generally low and below 1.3. The hydrophobic anchors were introduced into the lipid structures as initiators for the anionic polymerization of ethylene oxide and are either based on cholesterol or on different aliphatic glyceryl ethers. Complete incorporation of the apolar initiators was evidenced by MALDI-ToF analysis at all stage,, of the reaction, The linear-hyperbranched polyether lipid is incorporated as the polyfunctional shell in liposome formulation together with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The resulting liposomes Were Subsequently characterized via dynamic light scattering (DLS) and small angle neutron scattering (SANS) as well as transmission electron microscopy (TEM), demonstrating the formation of unilamellar liposomes in the size range of 40 to 50 nm
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