Polyethylene glycol (PEG) linkER is chemically functionalized polyethylene glycol linkers which attach to the sites of proteins by chemical linker. PEG linkER has drawn considerable interest and widely used in biological and medical studies due to their solubility in water, excellent biocompatibility and non-immunogenicity. PEG linkER has a great effect on the medical studies such as which can prolong circulation half-life, improved solubility and reduce proteolytic sensitivity. Moreover, the biomolecules modified with PEG linkER show increase resistance toward degradation in organisms, better pharmacokinetics, and the ability to cross the blood-brain barrier.


The PEG linkER is extensively applied to functional materials, biological and medical chemistry. The main applications of PEG linkER are as follows.

  • Modification of surface

PEG were used as a linker between the surface and the peptide for protease detection.[1] The nonspecific binding of peptide to the surface was reduced by introducing PEG linkER with hydrophilic. Given many proteolytic enzymes are active to specific peptide sequences, using the PEG-peptide surfaces as analytical platforms offers the opportunity for study of enzymatic activity.

The PEG-peptide surfaces as analytical platformsFigure 1. The PEG-peptide surfaces as analytical platforms

  • Cell carrier

It should be noted that the length of the PEG linkER plays a key role in regulating the uptake efficiency of nanoparticle. Inspired by this, the specific receptor binding of nanoparticle was evaluated by incorporation PEG linkER with different length to cyclic RGD ligand.[2] As a result, the nanoparticle with short PEG linkER displayed most efficient in targetin receptors in vitro and the overall entropic loss upon binding to receptor was reduced. A suitable length of the PEG linkER is important for biotherapy as cell carriers to maximize therapeutic efficacy and minimize undesired side effects.

The length of PEG linkER as cell carrier affects uptake efficiency of nanoparticleFigure 2. The length of PEG linkER as cell carrier affects uptake efficiency of nanoparticle

  • Fluorescence probe

NIR 4,4-difluoro-4-bora-3a,4a-diaza-sindacene (BODIPY) derivative was successfully conjugated to cetuximab and trastuzumab by the adding water-soluble group of PEG linkER.[3] Antibody conjugate display a high tumor to background ratios and persistent fluorescent signal, which suggest that the feasibility of NIR BODIPY conjugate as an activatable fluorescence probe for further clinical applications.

Fluorescent signal of NIR BODIPY derivative modified by PEG linkERFigure 3. Fluorescent signal of NIR BODIPY derivative modified by PEG linkER

  • Controlled drug release

The well-defined, water-soluble block- and gradient-type amine-functional PEG copolymer have been prepared by controlled anionic ring-opening copolymerization (AROcP).[4] More fundamentally, the copolymer exhibit thermo- and pH- responsive behavior in aqueous solution which are precisely tunable by the comonomer of PEG ratio. The amine-functional PEG-based copolymer have promising applications in controlled drug release due to PEG’s established biocompatibility and utilizing pH as their active trigger.

The amine-functional PEG copolymer controlled drug release utilizing pH as active triggerFigure 4. The amine-functional PEG copolymer controlled drug release utilizing pH as active trigger

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  1. Trzcinska R.; et al. Relevance of the poly(ethylene glycol) linkers in peptide surfaces for proteases assays. Langmuir 2014, 30(17): 5015-5025.
  2. Abstiens K.; et al. Ligand density and linker length are critical factors for multivalent nanoparticle–receptor interactions. ACS Appl. Mater. Interfaces 2019, 11(1): 1311-1320.
  3. Inagaki F. F.; et al. Effect of short PEG on near-infrared BODIPY-based activatable optical probes. ACS Omega 2020, 5(25): 15657-15665.
  4. Herzberger J.; et al. Stimuli-responsive tertiary amine functional PEGs based on N,N‑dialkylglycidylamines. Macromolecules 2014, 47(22): 7679-7690.
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