PEGlinkers

PEGlinkers, or poly(ethylene glycol) linkers, are polymer chains used as spacers and tethers in bioconjugation, surface modification, and nanoformulations. They are typically linear or branched polymers of repeating ethylene glycol units, terminated with functional groups that enable attachment to biomolecules, drugs, or surfaces. The length (molecular weight) and architecture (linear or multi-arm) can be tailored to adjust spacer distance, flexibility, solubility, and steric properties, as well as to influence pharmacokinetics and biodistribution in therapeutics.

Key properties include high water solubility, chemical stability, and biocompatibility. PEG linkers can reduce nonspecific interactions and proteolysis, and can confer “stealth” characteristics to nanocarriers. However, anti-PEG antibodies have been reported in some individuals, which can affect efficacy or safety and is an ongoing regulatory consideration. Polydispersity and batch-to-batch variability can also impact performance, particularly in clinical applications.

End groups and chemistries are diverse. Common functionalities include NHS esters and amines for amide coupling, thiol-reactive groups such as maleimide, and bioorthogonal handles like azides or alkynes for click chemistry. PEG linkers can be linear or branched (multi-arm) to modulate surface coverage and spacing. They are widely used in antibody-drug conjugates, protein and peptide conjugates, nanoparticle and surface functionalization, biosensors, ELISA blocking, and nucleic acid delivery systems.

Synthesis generally involves polymerizing ethylene oxide and subsequently installing the desired terminal group. PEGlinkers thus provide versatile, tunable spacers that improve solubility, biocompatibility, and functional presentation in a wide range of bioengineering and pharmaceutical applications.