Polyethylene Glycol (PEG) Selection Guide

What is Polyethylene Glycol?

Polyethylene glycol (PEG)

Polyethylene glycol (PEG), also sometimes referred to as polyethylene oxide (PEO), is a condensation polymer of ethylene oxide and water that has several chemical properties that make it useful for biological, chemical and pharmaceutical applications. Polyethylene glycol can be easily synthesized by the anionic ring opening polymerization of ethylene oxide into a range molecular weights and a variety of end groups, which enables PEG to be used in multiple research applications. When crosslinked into networks, PEG can have a high water content, forming hydrogels. Hydrogel formation can be initiated by crosslinking PEG by either ionizing radiation or by covalent crosslinking PEG macromers with reactive chain ends. Polyethylene glycol is a suitable material for biological applications because it does not initiate an immune response and is often used for protein precipitation and activated for binding to polypeptides and proteins.1,2

Polyethylene glycol is susceptible to oxidative degradation in the presence of air. Minimizing the exposure of PEG to elevated temperatures and exposure to oxygen, or adding an antioxidant can limit the amount of degradation. Polyethylene glycols do not hydrolyze or deteriorate upon storage and do not support the growth of molds. Polyethylene glycol is incompatible with phenol and may reduce the antimicrobial action of other preservatives. Polyethylene glycol rapidly inactivates penicillin and bacitracin and is incompatible with sorbitol, tannic acid and salicylic acid and may affect the integrity of plastics.3

How is Polyethylene Glycol used?

We offer PEG products suitable for multiple research applications, including molecular biology, hybridoma fusion, insect cell culture, gas chromatography stationary phase, analytical standards for GPC, peptide synthesis, x-ray crystallography, detergents and designer surfactants. Many of our PEGs are modified with functional or reactive termini for immobilization and conjugation to proteins, peptides and other macromolecules. These PEG reagents increase conjugate solubility and minimize toxic and immunological effects compared to non-PEG crosslinkers and modification reagents. Homobifunctional (identical reactive groups at either end) and heterobifunctional (different reactive groups at either end) PEG crosslinkers are offered with a variety of lengths and polymer architecture. Furthermore, both discrete and variable-length PEG crosslinking reagents are available.

Find the right PEG for Your Research Application

The hydrophilicity and biocompatibility of PEG makes it an excellent tool for polymer-based drug delivery and other biomedical applications. Linear and branched derivatives of PEG for pegylation and modification of peptides and proteins are used to reduce toxicity and immunogenicity and increase solubility and stability. There are four general characteristics to consider when selecting a PEG for drug delivery and biomedical research applications.

  • Monofunctional PEGs contain one chemically reactive end. Example applications include PEGylation, surface and nanoparticle coating.
  • Bifunctional PEGs contain two reactive ends, which can either be the same (homobifunctional PEG) or different (heterobifunctional PEG). Example applications include conjugation and crosslinking.
  • Covalent conjugation: PEGs with reactive end groups, such as an N-hydroxysuccinimide ester, thiol, or carboxyl group, can be covalently conjugated to corresponding functional groups. The conjugation chemistry chosen determines site of attachment and number of PEGs per molecule.
  • Click chemistry is a rapid, selective and bioorthogonal method for conjugation or network formation. Learn more about click chemistry.
  • PEG functionalized with a terminal acrylate are polymerizable by photopolymerization, which has a mild reaction condition and quick reaction time.
Polymer Architecture
  • Linear PEGs are commonly used for PEGylation, crosslinking, and conjugation in drug delivery systems
  • Multi-arm PEGs  (4-,6-,8-arm) can be crosslinked into hydrogels and scaffolds for drug delivery or tissue engineering applications
  • Y-shaped PEGs are used for PEGylation because the branched structure improves stability in vivo.
Molecular Weight
  • PEGylation: High molecular weight PEGs (≥5 kDa) are used for conjugation to low molecular weight drugs (e.g., small molecules and siRNA). Low molecular weight PEGs (≤5 kDa) are used for PEGylation to high molecular weight proteins and peptides.
  • Hydrogel formation: Molecular weight will influence the hydrogel mesh size and mechanical properties. Typically, high molecular weight PEGs (≥5 kDa) are used.

Covalent modification with PEG groups requires compounds that contain a reactive group or a targetable functional group on at least one end. A functional group refers to a group of atoms in a molecule that have characteristic chemical reactions regardless of the rest of the molecule. Some of the common functional groups and their corresponding reactive groups are listed in the table below.

Functional Groups Reactive Groups
Primary Amine (–NH2) NHSEster

Sulfonyl Chloride
Acyl Azide
Fluorophenyl Ester
Thiol (–SH) Maleimide
Pyridyl disulfide
Carboxyl (–COOH) Carbodiimide Compounds (EDC, DCC)  
Carbonyl (–CHO) Hydrazides Alkoxyamines  


1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride)





  1. Ingham, K.C., Precipitation of Proteins with Polyethylene Glycol. Meth. Enzymol., 182, 301-306 (1990).
  2. Veronese, F.M., et al., Surface modification of proteins. Activation of monomethoxy-polyethylene glycols by phenylchloroformates and modification of ribonuclease and superoxide dismutase. Appl. Biochem. Biotechnol., 11, 141-152 (1985).
  3. Martindale, W. The Extra Pharmacopoeia, 30th ed., Reynolds, J. E. F., ed., The Pharmaceutical Press (London, England: 1993), p. 1384.

 General Reference

  •  Hermanson, G.T., Bioconjugate Techniques 3rd Edition, Academic Press (2013).