PEGylation Chemistry

The introduction of a PEG linker to a molecule provides many benefits for pharmaceutical and biotech R&D due to its water solubility, lower toxicity and non-immunogenicity.

The introduction of different functional groups to the end of a PEG linker allows for more site-specific reactions. For example, proteins have various amino acid residue that may be involved in chemical reactions with amine, sulfhydryl, carboxyl and carbonyl groups being more likely to be targeted for bioconjugation. By altering the end group of the PEG linkers, it is easier to target these amino acid residues or specific functional groups. Table 1 lists reactive groups and available PEG linkers that can be used to target these reactive groups. 

Table 1: Reactive groups and corresponding activated PEG linkers
Reactivity ClassPEG Linkers
PEG Acid
PEG Aldehyde
PEG NHS ester
PEG PFP ester
CarbonylAminooxy PEG
Carboxyl and Active EsterAmino PEG
Click Chemistry Alkyne PEG
PEG azide
Copper Free Click ChemistryBCN-PEG
Tetrazine PEG
Thiol ReactiveBromo PEG

Modified PEG linkers can be used for different applications. In some instances, reaction conditions must be altered so that proteins are able to properly react with the PEG reagent. Below are some common PEGylation chemistry reactions.

Aldehyde Conjugation

PEG aldehyde can be used in bioconjugation due to reactions between aminooxy or hydrazide moiety.

Figure 1: Reaction scheme of PEG aldehyde chemistry.


Figure 2: Reaction scheme of amino PEG chemistry.


Thiol Conjugation

PEG Thiols are reactive with maleimides, disulfides, haloacteamides and other types of thiols. They can also be involved in metal surface binding.

Figure 3: Reaction scheme of thiol PEG chemistry.


Click Chemistry

Click chemistry describes a wide variety of reactions that occur between two reactive functional groups that can attach to one another under milder, aqueous conditions. Click chemistry tools have improved over the years. First generation click chemistry tools involved copper-catalyzed reactions of terminal alkyne and azide groups. Second generation click chemistry tools made use of strain-promoted alkyne azide reactions without being copper-catalyzed. Third generation Click Chemistry involves the reaction between tetrazine and alkenes such as trans-cyclooctene.

Figure 5: Second generation Click Chemistry involves strain-promoted reactions between azides and alkynes with no Cu(I) catalyst.

Figure 6: Third generation Click Chemistry between tetrazine and an alkene to promote strain-induced reactions. This reaction occurs very quickly and works without a Cu(I) catalyst.


BroadPharm has over 2,000 PEG linkers in stock to fit the needs of our customers. Please visit our website at to learn about the applications of each of our PEG linkers.