ABSTRACT
Biotinylated polymers with side-chain aldehydes were prepared for use as multifunctional scaffolds. Two different biotin-containing chain transfer agents (CTAs) and an aldehyde-containing monomer, 6-oxohexyl acrylate (6OHA), are synthesized. Poly(ethylene glycol) methyl ether acrylate (PEGA) and 6OHA are copolymerized by reversible addition-fragmentation chain transfer (RAFT) polymerization in the presence of the biotinylated CTAs. The resulting polymers are analyzed by GPC and(1) H NMR spectroscopy. The polymer end groups contained a disulfide bond, which could be readily reduced in solution to remove the biotin. Reactivity of the aldehyde side chains is demonstrated by oxime and hydrazone formation at the polymer side chains, and conjugate formation of fluorescently labeled polymers with streptavidin is investigated by gel electrophoresis.
Subject(s)
Aldehydes/chemistry , Biocompatible Materials/chemical synthesis , Biotin/chemistry , Polymers/chemical synthesis , Biocompatible Materials/chemistry , Biotinylation , Molecular Structure , Polymerization , Polymers/chemistry , Streptavidin/chemistryABSTRACT
Toxicity of poly(ethylene glycol acrylate) (poly(PEGA)) synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using different chain transfer agents (CTA)s is described.
Subject(s)
Acrylates/chemistry , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/toxicity , Animals , Cell Proliferation/drug effects , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , NIH 3T3 Cells , Polyethylene Glycols/chemistryABSTRACT
Ionomers containing sodium 4-styrene sulfonate (4SS) and poly(ethylene glycol) methyl ether acrylate (PEGA) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymerization was mediated by 1-phenylethyl dithiobenzoate chain transfer agent in a dimethylformamide/water solvent system. Well-defined copolymers of pPEGA-co-4SS were produced with molecular weights ranging from 10 kDa to 40 kDa and polydispersity indices (PDIs) of 1.06-1.18 by gel permeation chromatography (GPC) against monodisperse poly(methyl methacrylate) (PMMA) standards. Post polymerization, the dithioester was reduced and trapped in situ with divinyl sulfone to produce a well-defined, semitelechelic pPEGA-co-4SS Michael acceptor polymer. UV-vis, infrared, and (1)H NMR spectroscopy confirmed that the integrity of the polymer backbone was maintained and that the vinyl sulfone was successfully incorporated at the chain end.
ABSTRACT
Herein we report the synthesis of vinyl sulfone end functionalized PEGylated polymers by reversible addition-fragmentation chain transfer (RAFT) polymerization for conjugation to proteins. Poly(ethylene glycol) methyl ether acrylate (PEGA) was polymerized in the presence of 1-phenylethyl dithiobenzoate with 2,2'-azobis(2-methylpropionitrile) as the initiator to generate well-defined polyPEGAs with number-average molecular weights (M(n)) by gel permeation chromatography (GPC) of 6.7 kDa, 11.8 kDa and 16.1 kDa. Post-polymerization, the majority of polymer chains contained the dithioester functional group at the omega chain end, and the polydispersity indexes (PDI) of the polymers ranged from 1.08 to 1.24. The dithioester was subsequently reduced via aminolysis, and the resulting thiol was trapped with a divinyl sulfone in situ to produce semi-telechelic, vinyl sulfone polyPEGAs with efficiencies ranging between 85% and 99%. It was determined that the retention of vinyl sulfone was directly related to reaction time, with the maximum dithioester being transformed into a vinyl sulfone within 30 minutes. Longer reaction times resulted in slow decomposition of the vinyl sulfone end group. The resulting semi-telechelic vinyl sulfone polymers were then conjugated to a protein containing a free cysteine, bovine serum albumin (BSA). Gel electrophoresis demonstrated that the reaction was highly efficient and that conjugates of increasing size were readily prepared. After polymer attachment, the activity of the BSA was 92% of the unmodified biomolecule.
Subject(s)
Alcohols/chemistry , Fluorine/chemistry , Fluorocarbons/chemistry , Carbohydrates/chemistry , Cholecalciferol/chemistry , Crystallography, X-Ray , Magnesium/chemistry , Methane/analogs & derivatives , Methane/chemistry , Methylation , Models, Molecular , Molecular Structure , Stereoisomerism , Sulfones/chemistryABSTRACT
The synthesis of alpha-aminonitriles and their fluorinated analogs has been carried out in high yield and purity by the Strecker reaction from the corresponding ketones and amines with trimethylsilyl cyanide using gallium triflate in dichloromethane. Monofluoro-, difluro-, or trifluoromethyl groups can be incorporated into the alpha-aminonitrile product by varying the nature of the fluorinated ketones. Study with various fluorinated and nonfluorinated ketones reveals that the choice of proper catalyst and the solvent system (suitable metal triflates as a catalyst and dichloromethane as a solvent) plays the key role in the direct Strecker reactions of ketones.
