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What Is dPEG®?

The term dPEG® is Vector Laboratories’ trademarked acronym for “discrete polyethylene glycol” or “discrete PEG”. The “discrete” portion of the dPEG® trademark indicates single molecular weight PEG technology. Like traditional PEGs, our products contain an amphiphilic[1] backbone of repeating ethylene oxide units. However, traditional PEGs are not single compounds. Quanta Biodesign, now part of Vector Laboratories, invented and manufactures these monodisperse PEG products using our proprietary synthetic and purification processes.

What is PEGylation?

PEGylation is the process of adding polyethylene glycol (PEG) to a molecule or surface, often through covalent modification of the targeted molecule or surface. Molecules and surfaces that have been modified by PEGylation are called PEGylated. Any surface containing appropriate functional groups can be PEGylated. Gold, silver, iron, and silica are examples of surfaces that are often PEGylated for use in diagnostic, therapeutic, or theranostic applications. The list of molecules that are PEGylated is enormously long and continually expanding. Examples of the types of molecules that are PEGylated include small molecule therapeutic drugs, peptides, proteins, the carbohydrate coats of glycoproteins, oligonucleotides, and lipids.

The benefits of PEGylation include increased water solubility, increased hydrodynamic volume, decreased immunogenicity, and extended circulation in vivo in the bloodstream due to reduced renal clearance. In addition to reducing renal clearance, PEGylation also often modifies the biodistribution and pharmacokinetics of therapeutic, theranostic, and diagnostic molecules.

Traditional PEGs

Specifically, traditional PEG products are prepared by polymerization processes. Any polymerized PEG product is a Poisson distribution of chain lengths and molecular weights.[2], [3] This distribution was formerly known as the polydispersity index (PDI), but is now known as the dispersity index or simply dispersity (indicated by the symbol “Đ”)[4]. The reported molecular weight is an average molecular weight, and Đ (or PDI) gives an indication of the range of molecular weights in the sample. Disperse samples have Đ > 1 and are a heterogeneous mixture of sizes and molecular weights. High M.W. (>50 kDa) traditional PEG has Đ up to 1.1. Lower M.W. traditional PEG has Đ in the range of 1.01 – 1.05. These numbers represent broad distributions of molecular weights.[5], [6], [7]

dPEG® Products Are Different

Our dPEG® products are quite different from traditional PEGs, because of our proprietary, patent-protected processes. Each dPEG® product represents a single compound with a unique, specific, single molecular weight (MW). See Figure 1.
Figure 1

Side-by-side mass spectra of traditional polyethylene glycol (PEG) and a dPEG® of equivalent mass from Vector Laboratories

side by side dpeg comparison color
side by side dpeg comparison color 02
Figure 1: Side-by-side comparison of actual mass spectra from a traditional, dispersed PEG (left spectrum) and a dPEG® of equivalent mass from Vector Laboratories (right spectrum). The mass spectrum on the left is of PEG1000. It has Mw = 1027 Daltons; Mn = 888 Daltons; and Đ = 1.16. The masses in this dispersed PEG range from 600 – 1,500 Daltons. The mass spectrum on the right is of Vector Laboratories product number QBD-10317, amino-dPEG®24-acid, the structure of which is shown across the top of the two mass spectra. QBD-10317 is a single molecular weight compound with a single, discrete chain length. The molecular weight of QBD-10317 is 1146.355 Daltons. Because it has no dispersity, Đ = 1.

A Wide Variety of Functional Groups and Architectures for dPEG® Products

Our dPEG® products are synthesized from high purity building blocks (e.g. diethylene glycol, triethylene glycol, or tetraethylene glycol) in a series of stepwise reactions to provide specific MWs, organic moieties, functional groups (see Figure 2), and architectures (see Figure 3) suited for a wide variety of applications. From these building blocks, we produce homobifunctional and heterobifunctional crosslinkers, homotetrafunctional crosslinkers, biotinylation reagents, fluorescent tags, surface modification reagents, and specialized products designed for modification of pharmacokinetics (PK) and biodistribution (BD). Our products contain methoxy, alcohol, and carboxylic acid end-capping; various protective groups for reactive moieties (e.g., methoxytrityl, Fmoc, boc, etc.); various functional groups for conjugation to amines, thiols, alcohols, carboxylic acids, ketones, aldehydes, alkynes, and azides; and a wide variety of organic moieties (i.e., biotin, lipoamide, fluorescein, DOTA, etc.).
Figure 2
Functional/Reactive Groups for dPEG® Products
Click Chemistry Functional Groups with dPEG® Linkers/Spacers
Labeling Groups with dPEG® Linkers/Spacers
Other labels are also available!
DOTA dPEG® Products with Various Functional Groups
Protective Groups for dPEG® Products
Figure 2: Examples of the functional, reactive, labeling, and protective groups on dPEG® products.
Figure 3







Figure 3: Available architectures for dPEG® products. Branched dPEG® products can have three (3) or nine (9) branches. Our Sidewinder™ products are a new class of dPEG® constructs that offer a broad range of new ways to incorporate dPEG® functionality into diagnostic and therapeutic applications. The BodyArmor® product architecture is similar to the Sidewinder, but includes additional orthogonal dPEG® strands.
All dPEG® products contain linear chains of two to seventy-two ethylene oxide units. We also build branched structures consisting of three to nine of these linear chains. Our proprietary synthetic processes maintain the homogeneity of our products in the range of 200 Da to 16 kDa. Our Sidewinder™ line of products was designed by Quanta Biodesign, now part of Vector Laboratories, scientists to provide new ways to incorporate the beneficial properties and advantages of dPEG® products into diagnostic and therapeutic applications. One clear application for these products is fine-tuning PK and BD of diagnostic and therapeutic products. These novel dPEG® products are not possible with traditional disperse PEG products.
Further Reading: If you want to read our answers to the questions we are asked most often about dPEG® products, please click here.
  1. The term “amphiphilic” means that the compound is soluble in both water (or aqueous buffer) and organic solvents. All PEG products that do not contain hydrophobic substituents are soluble in water and in a variety of organic solvents. The addition of hydrophobic groups to PEG reduces the water solubility of some PEG products.
  2. Flory, P. J. Molecular Size Distribution in Ethylene Oxide Polymers. J. Am. Chem. Soc. 1940, 62, 1561−1565. [ACS Publications]
  3. Herzberger, J.; Niederer, K.; Pohlit, H.; Seiwert, J.; Worm, M.; Wurm, F. R.; Frey, H. Polymerization of Ethylene Oxide, Propylene Oxide, and Other Alkylene Oxides: Synthesis, Novel Polymer Architectures, and Bioconjugation. Chem. Rev. 2016, 116, 2170-2243. [ACS Publications]
  4. Gilbert, R. G.; Hess, M.; Jenkins, A. D.; Jones, R. G.; Kratochvíl, P.; Stepto, R. F. T. Dispersity in polymer science (IUPAC Recommendations 2009). Pure Appl. Chem. 2009, 81, 351–353. [De Gruyter]. See also, Stepto, R. F. T. Erratum. Pure Appl. Chem. 2009, 81, 779. [De Gruyter]
  5. Veronese, F. M.; Mero, A.; Pasut, G. Protein PEGylation, Basic Science and Biological Applications. In PEGylated Protein Drugs: Basic Science and Clinical Applications; Veronese, F. M., Ed.; Milestones in Drug Therapy; Birkhäuser Basel: Basel, 2009; pp 11–31. [Springer]
  6. Jevsevar, S; Kunstejl, M; Porekar, V.G. PEGylation of therapeutic proteins. Biotechnology Journal 2010, 5(1) 113-128. DOI: [Wiley]
  7. For example, dextran with Đ=2 is considered “low dispersity” today. Previously dextran had even higher dispersity than that. See, Pasut, G. Polymers for Protein Conjugation. Polymers 2014, 6(1), 160–178. [MDPI]