6533b7d0fe1ef96bd125a44c
RESEARCH PRODUCT
Cleavable Polyethylene Glycol: 3,4-Epoxy-1-butene as a Comonomer to Establish Degradability at Physiologically Relevant pH.
Carsten DingelsDaniel LeibigMatthias WormHolger Freysubject
Materials sciencePolymers and Plasticsmacromolecular substances02 engineering and technologyPolyethylene glycol010402 general chemistry01 natural sciencesInorganic Chemistrychemistry.chemical_compoundPEG ratioPolymer chemistryMaterials ChemistrymedicineOrganic chemistryPropenylEthylene oxideComonomerOrganic Chemistrytechnology industry and agriculture1-ButeneVinyl ether021001 nanoscience & nanotechnology0104 chemical scienceschemistryPolymerization0210 nano-technologymedicine.drugdescription
Polyethylene glycol (PEG) has been used for decades to improve the pharmacokinetic properties of protein drugs, and several PEG-protein conjugates are approved by the FDA. However, the nondegradability of PEG restricts its use to a limiting molecular weight to permit renal excretion. In this work, we introduce a simple strategy to overcome the nondegradability of PEG by incorporating multiple pH-sensitive vinyl ether moieties into the polyether backbone. Copolymerization of 3,4-epoxy-1-butene (EPB) with ethylene oxide via anionic ring-opening polymerization (AROP) provides access to allyl moieties that can be isomerized to pH-cleavable propenyl units (isoEPB). Well-defined P(EPB-co-EG) copolymers (Đ = 1.05–1.11) with EPB contents of ∼4 mol% were synthesized in a molecular weight range of 3000 to 10000 g mol–1. 1H NMR kinetic studies served to investigate acidic hydrolysis in a pH range of 4.4 to 5.4 and even allowed to distinguish between the hydrolysis rates of (E)- and (Z)-isoEPB units, demonstrating fa...
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-11-28 | ACS macro letters |