The dPEG® Linker Platform for BioDesign™ of Bioconjugate Therapeutics
Introduction
Explore the dPEG offerings from Vector Laboratories
Array of dPEG based products for research and development —
Numerous synthetic technologies, chemistry expertise and deep familiarity with customer needs have enabled Vector Laboratories to develop a broad portfolio of PEG product lines that are diverse, highly pure, and scalable.
- Homo-, hetero-, and multifunctional crosslinking reagents for conjugating biologics, payloads, carriers, and surfaces.
- A wide variety of reactive groups for conjugation strategies including click chemistry, biorthogonal, site-specific, enzymatic, and stochastic approaches.
- Building blocks & intermediates for flexible linker architecture design.
- Chemical modification reagents with a variety sizes, architectures, and end capping.
- Block copolymers for polymeric and lipid nanoparticles.
- Affinity tags including biotin, lipids, and haptens.
- Fluorophores with increased hydrophilicity.

Click Chemistry Reactive Groups with dPEG® Linkers/Spacers

Labeling Groups with dPEG® Linkers/Spacers

DOTA dPEG® Products with Various Functional Groups

Protective Groups for dPEG® Products

Linker Architectures

Homobifunctional

Heterobifunctional

Sidewinder™

Branched

Tetramer

Hexamer


Scaffolded
Comparison of traditional PEGs with dPEGs
The first clinical applications of large, polydisperse, traditional PEGs in drug development were the PEGylation of proteins, peptides, and enzymes (Oncaspar, Adagen, Peg-Intron, etc.) to improve their drug metabolism and pharmacokinetic (DMPK) properties. This strategy of altering the physiochemical (PC) or DMPK properties by the covalent attachment of PEG is now used for several therapeutic modalities including antibody fragments, peptides, small molecules, oligonucleotides, and nanoparticles.
The dPEGs or uniform PEGs from Vector Laboratories can be used to further optimize the PC and adsorption, distribution, metabolism, elimination, and toxicity (ADMET) properties of a therapeutic, to achieve targeting, solubility and stability requirements. Table 1 shows a few advantages of uniform PEGs over traditional PEGs.
Traditional Polydisperse PEGs | dPEGs |
---|---|
Lower purity with multiple MW entities | Highly pure with a single MW entity (see Fig. 3) |
Manufactured by a polymerization process | Manufactured by a proprietary process |
Complex to analyze due to multiple entities | Straightforward analysis |
Limited design opportunities due to multiple entities | Infinite design possibilities for bioconjugation tools |
Limited flexibility of BD, PD and PK property modulation for any bioconjugate constructs | High flexibility for optimization of BD, PD and PK properties in all bioconjugate constructs due to design and manufacture controls |


Wide Variety of Applications with dPEGs —
Due to the unique combination of biocompatibility, uniformity, and
designability, dPEGs can be used to impart favorable properties in a
wide variety of applications including:
- Linkers for conjugates such as antibody drug conjugates (ADCs), fragment drug conjugates (FDCs), protein drug conjugates (PDCs), small molecule drug conjugates (SMDCs), oligo conjugates (OCs), and drug delivery systems (DDS), without the hydrophobic liabilities of alkyl linkers and ambiguity of polydisperse linkers (see Table 2).
- Spacers and spatial modifiers, to explore and optimize proximity effects with a high degree of flexibility.
- Surface modifiers to alter size, shape, charge, hydrophobicity, permeability, and impart stimuli or temporal dependent qualities in small molecules, oligonucleotides, peptides, proteins, antibodies, polymers, dendrimers, lipid nanoparticles, and inorganic surfaces/nanoparticles.
Property | Polydisperse PEG | Alkyl cross linker | Sulphonated cross Linker |
Uniform PEG |
---|---|---|---|---|
Purity | + | ++++ | ++++ | ++++ |
Manufacture process | Polymerization | Synthetic | Synthetic | Proprietary |
Analysis | Complex due to multiple entities |
Simple | Simple | Simple |
Flexibility of Design | + | + | + | ++++ |
Flexibility of modulation of PK, PD properties in bioconjugate constructs | + | + | + | ++++ |
Hydrophilicity | + | + | + | ++++ |
Ability to shield hydrophobic moieties | + | + | + | ++++ |
dPEGs as Linkers
Small molecule conjugates
There are several studies that document the advantages of using dPEGs to link small molecules to imaging agents for diagnostic applications. For instance, when folate dimers labelled with fluorescein were prepared with 2 kDa PEG, 1 kDa PEG, or dPEG24 crosslinkers,
Peptide Conjugates

Oligo Conjugates
Delivery has become the major hurdle for oligos, and as such several conjugates have been designed as delivery systems that incorporate
Degraders and Degrader Conjugates
Proximity-induced degradation is a promising new modality for drugging the undruggable targets, and PROTACs are one of the more popular classes of degraders.
Fragment Conjugates

Antibody Conjugates

NP Conjugates

Covalent Attachment of dPEGs as Modifiers of PC and ADMET Properties
Antibody fragments

Peptides
PEGylation or covalent attachment of PEGs to peptides, remains an attractive approach for improving DMPK properties of peptides. Some peptide-PEG conjugates currently in clinical trials include exenatide,
Small molecules
Early preclinical studies generally employed large PEG as a carrier to prolong the half-life of small molecules
Oligonucleotides (ONs)

Nanoparticles (NPs) and Drug Delivery Systems

dPEG at the crossroads of Chemistry and Biology
In conclusion, the dPEG technology is at the foundation of numerous bioconjugate therapeutics and clinical diagnostic assays. Numerous publications have showcased the utility of dPEG based linkers and cited better target specificity, improved tumor uptake and lower toxicities with such linkers.
Overall, the competitiveness of using dPEG as linkers, modifiers, block co-polymers or functional tags lies in its discreteness, which is not available with traditional PEG.
Vector Laboratories has the deep technical expertise and manufacturing capabilities to help you design and develop unique dPEG based entities for integration within your conjugation strategy. With the BioDesign service, we can provide you with personalized, expert guided consultation, that can take your bioconjugate therapeutics to the next level.
References
- Jinming Hu., Shiyong Liu., et al. (2022). Emerging trends of discrete Poly(ethylene glycol) in biomedical applications. Curr Opin Biomed Eng, V. 24(100419), 2468-4511. [ScienceDirect]
- Quiles S., Raisch K.P., Sanford L.L., Bonner J.A., Safavy A., et al. (2010). Synthesis and preliminary biological evaluation of high-drug-load paclitaxel-antibody conjugates for tumor-targeted chemotherapy. J. Med. Chem., 53(2), 586-94. [Dataset]
- Giese M.W., Woodman R.H., Hermanson G.T., Davis P.D., et al. (2021). Chapter 9: The Use of Uniform PEG Compounds in the Design of ADCs. The Royal Society of Chemistry, ch. 9, 286-376. [The Royal Society of Chemistry]
- Tiberghien A.C., Levy J.N., Masterson L.A., Patel N.V., Adams L.R., Corbett S., Williams D.G., Hartley J.A., Howard P.W., et al. (2016). Design and Synthesis of Tesirine, a Clinical Antibody-Drug Conjugate Pyrrolobenzodiazepine Dimer Payload. ACS Med Chem Lett., 7(11), 983-987. [PubMed]
- Giese M., Davis P.D., Woodman R.H., Hermanson G., Pokora A., Vermillion M. et al. (2021). Linker Architectures as Steric Auxiliaries for Altering Enzyme-Mediated Payload Release from Bioconjugates. Bioconjugate Chemistry, 32(10), 2257-2267. [ACSPub]
- Tang G. Q., Tang Y., Dhamnaskar K., Hoarty M.D., Vyasamneni R., Vadysirisack D.D., Ma Z, Zhu N., Wang J.G., Bu C., Cong B., Palmer E., Duda P.W., Sayegh C., Ricardo A., et al. (2023). Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation. Front Immunol., 14, 1213920. [PubMed]