Polyethylene Glycol (PEG) Selection Guide

What is Polyethylene Glycol?

Polyethylene glycol (PEG)

Poly(ethylene glycol) (PEG) is a synthetic, hydrophilic, biocompatible polymer with widespread use in biomedical and other applications. PEGs are synthesized using a ring-opening polymerization of ethylene oxide to produce a broad range of molecular weights and molecular weight distributions (polydispersity); however, discrete PEGs (dPEG®) are synthesized with a single, specific molecular weight.  PEGs can be synthesized in linear, branched, Y-shaped, or multi-arm geometries. PEGs can be activated by the replacement of the terminal hydroxyl end group with a variety of reactive functional end groups enabling crosslinking and conjugation chemistries.


How is Polyethylene Glycol used?

PEGs are non-toxic, FDA-approved, generally nonimmunogenic, and are frequently used in many biomedical applications including bioconjugation,1 drug delivery,2,3  surface functionalization,4 and tissue engineering.5  Bioconjugation with PEG (also known as PEGylation) is the covalent conjugation of drug targets such as peptides, proteins, or oligonucleotides with PEG for the optimization of pharmacokinetic properties.6  In drug delivery, PEGs can be used as linkers for antibody-drug conjugates (ADCs)7 or as a surface coating on nanoparticles to improve systemic drug delivery.6 PEG hydrogels are water-swollen, three-dimensional, polymer networks resistant to protein adhesion and biodegradation.8 PEG hydrogels are produced by crosslinking reactive PEG end groups and are commonly used in tissue engineering and drug delivery.

Find the right PEG for Your Research Application

Four general characteristics should be considered when selecting PEGs for bioconjugation, drug delivery and tissue engineering research applications:


  • Monofunctional PEGs contain a single chemically-reactive end and are used for PEGylation, surface conjugation, and nanoparticle coating.
  • PEGs containing two reactive ends, which can either have the same (homobifunctional PEG) or different (heterobifunctional PEG) reactive groups are useful for conjugation and crosslinking for hydrogels


  • 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 requires PEGs with azide or alkyne reactive groups. Click chemistry is a rapid, selective, and bioorthogonal method for conjugation or hydrogel formation. Learn more about click chemistry.
  • Polymerization and photopolymerization can be achieved rapidly using acrylate-terminated PEGs under mild reactive conditions

Polymer Architecture

  • Linear PEGs are commonly used for PEGylation, bioconjugation, and crosslinking
  • Multi-arm PEGs  (4-,6-,8-arm) can be crosslinked into hydrogels and scaffolds for drug delivery or tissue engineering
  • Y-shaped PEGs are typically used for PEGylation, as the branched structure may improve stability in vivo.

Molecular Weight

  • Bioconjugation:  PEGs with molecular weights ≥5 kDa are typically used for conjugation to small molecules, siRNA, and peptides. Low molecular weight PEGs (≤5 kDa) are often used for PEGylation of proteins.
  • Surface conjugation and crosslinking can be completed with PEGs that are < 40 kDa
  • Hydrogel formation: PEG molecular weight will influence the hydrogel mesh size and mechanical properties. Typically, PEGs ≥5 kDa molecular weight are used.

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) Amines    
Carbonyl (–CHO) Hydrazides Alkoxyamines  


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





  1. Hermanson, G. T. Bioconjugate Techniques; Elsevier Science: Burlington, 2013.
  2. POLYMERIC DRUG DELIVERY TECHNIQUES: Translating Polymer Science for Drug Delivery; Aldrich Materials Science: Milwaukee, WI, 2015.
  3. Parveen, S.; Sahoo, S. K. Eur. J Pharmacol. 2011670 (2-3), 372–383.
  4. Manson, J.; Kumar, D.; Meenan, B. J.; Dixon, D. Gold Bull. 201144 (2), 99–105.
  5. Fairbanks, B. D.; Schwartz, M. P.; Bowman, C. N.; Anseth, K. S. Biomaterials 200930 (35), 6702–6707.
  6. Suk, J. S.; Xu, Q.; Kim, N.; Hanes, J.; Ensign, L. M. Adv. Drug Deliv. Rev. 201699, 28–51.
  7. Jain, N.; Smith, S. W.; Ghone, S.; Tomczuk, B. Pharm. Res. 201532 (11), 3526–3540.
  8. Hoffman, A.S. Adv. Drug Deliv. Rev. 200254(1), 3-12.