Affinity-Directed Dynamics of Host-Guest Motifs for Pharmacokinetic Modulation via Supramolecular PEGylation.

ABSTRACT: Proteins are an impactful class of therapeutics but can exhibit suboptimal therapeutic performance, arising from poor control over the timescale of clearance. Covalent PEGylation is one established strategy to extend circulation time but often at the cost of reduced activity and increased immunogenicity. Supramolecular PEGylation may afford similar benefits without necessitating that the protein be permanently modified with a polymer. Here, we show that insulin pharmacokinetics can be modulated by tuning the affinity-directed dynamics of a host-guest motif used to non-covalently endow insulin with a poly(ethylene glycol) (PEG) chain. When administered subcutaneously, supramolecular PEGylation with higher binding affinities extends the time of total insulin exposure systemically. Pharmacoki

SUBMITTER: Maikawa CL 

PROVIDER: S-EPMC8627827 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature