PEG Linkers & Applications Highlight
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There
are two classes of PEG linkers, Monodispersed and Poly-dispersed. Monodispersed
PEG has an exact number of PEG units with a specific, single
chemical structure with precise molecular weight, as
exemplified by Azido-PEG12-NHS ester (Figure
1). Whereas poly-dispersed PEG is a polymer mixture that has
an average molecular weight.
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Figure
1. Azido-PEG12-NHS ester is a bifunctional,
monodisperse PEG linker.
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In the
last two decades, PEG linkers have become
widely used in pharmacological and biotechnological R&D such as antibody drug conjugates (ADC),
Drug discovery & drug delivery because of their water
solubility, lack of toxicity, low immunogenicity. A few
Applications are highlighted as below:
PEG Linker in Antibody Drug Conjugate (ADC)
ADC drug, Zynlonta incorporated several
interesting linker components (Figure 2). The linker includes
the maleimide - PEG8, and enzymatically cleavable
dipeptide (Val-Ala), to connect the antibody with the payload.
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Figure
2. Zynlonta has several unique features including a maleimide
group for attachment to the mAbs, a PEG8 liner for solubility, and a
cleavable Val-Ala section bound to the drug SG3199.
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PEG Lipid in Nanoparticle Drug Delivery
Stable nucleic acid lipid
particles (SNALPs) were first developed in 2001. They have now
become famous with the development of Moderna and Pfizer COVID-19
vaccines (Figure 3). Typically, SNALPS are composed of a high
transition temperature phospholipid, a PEG lipid, and an ionizable phospholipid. One
specific example is DSPE-mPEG 2000, which is essential
to producing the Pfizer COVID-19 vaccine. Another well-known
PEGylated lipid is DMG-PEG 2000, is used in the
Moderna COVID-19 vaccine.
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Figure
3. PEG Lipids used in COVID-19 vaccines, Pfizer’s DSPE-PEG
2000 shown on top and Moderna’s DMG-PEG 2000 shown on bottom.
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PEG in Small Molecule Drug Development
Introduction of PEG linkers
to small molecule drugs increases the drug's solubility and
molecular weight. This may allow for an extended drug half-life in
the body. Naloxegol (Movantik) is one example of a small molecule
drug that incorporates PEG to improve the drug’s efficiency by
reducing its transport across the blood-brain barrier (Figure 4).
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Figure
4. Movantik, shown above, is a pegylated derivative of
α-naloxol.
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As a
worldwide leader of PEG linkers & Bioconjugation reagent,
BroadPharm offers a wide array of PEG Linkers to empower our
customer’s advanced research. These compounds feature great aqueous
solubility, smart choice of PEG length, and a broad selection of
functional groups to choose from. Please email to sales@broadpharm.com, or call,
+1-858-677-6760, with any questions you may have.
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