DSPE-PEG(5000) DBCO A88226 (Legacy code 880226) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[dibenzocyclooctyl(polyethylene glycol)-5000] (ammonium salt)

DSPE-PEG(5000) DBCO is a PEGylated phospholipid designed for copper-free surface conjugation on liposomes and lipid nanoparticles (LNPs). The lipid combines a DSPE anchor with a 5,000 Da PEG spacer and a terminal dibenzocyclooctyne (DBCO) group, creating a straightforward route to bioorthogonal functionalization after particle formation.

The DBCO moiety participates in strain-promoted azide-alkyne cycloaddition (SPAAC), a click chemistry reaction that proceeds under aqueous, near-physiological conditions. Because the reaction does not require copper catalysts, UV exposure, or aggressive reagents, it is well-suited for sensitive biological materials and complex formulation workflows. The resulting triazole linkage is highly stable, supporting durable biomolecule attachment.

Why PEG5000 vs. PEG2000? In most cases, researchers choose PEG2000 (see DSPE-PEG(2000) DBCO) when direct ligand presentation is the primary goal of their studies.

Alternatively, DSPE-PEG(5000) DBCO is generally chosen when formulations require a longer PEG spacer, increased steric shielding, or a greater separation distance between the nanoparticle surface and an attached targeting moiety. These characteristics can be particularly valuable for in vivo applications, prolonged circulation strategies, and two-tier architectures in which ligands are displayed beyond the protective PEG layer.

This product is available from Avanti Research™ in 5 mg powder packaging.

Application

DSPE-PEG(5000) DBCO is commonly incorporated into liposomal and LNP formulations before being reacted with azide-functionalized ligands on the finished particle surface. That post-formulation strategy enables flexible modification without disrupting nanoparticle assembly.

Researchers have used this approach to attach a wide range of targeting and functional molecules, including antibodies, Fab fragments, peptides, aptamers, oligonucleotides, fluorescent probes, and small-molecule ligands. Conceptually similar SPAAC-based strategies using DBCO-modified liposomes and LNPs have been reported, including antibody-conjugated vesicles for targeting, copper-free click conjugation of single-chain fragments and full antibodies for vascular targeting, and metabolic glycoengineering–driven conjugation of LNPs to azide-modified T cell surfaces for cell therapy applications.

Key features

• Copper-free SPAAC click chemistry for selective azide coupling
• Bioorthogonal reaction conditions compatible with live cells, proteins, and in vivo systems
• Extended PEG5000 stealth chain for prolonged circulation and stronger steric shielding
• >99% purity for reproducible formulation and conjugation studies

References

Gai, Meiyu, et al. “A Bio-Orthogonal Functionalization Strategy for Site-Specific Coupling of Antibodies on Vesicle Surfaces after Self-Assembly.” Polymer Chemistry, vol. 11, no. 2, 2020, pp. 527–540, pubs.rsc.org/en/content/articlehtml/2020/py/c9py01136f, https://doi.org/10.1039/c9py01136f

 Hood, Elizabeth D., et al. “Vascular Targeting of Radiolabeled Liposomes with Bio-Orthogonally Conjugated Ligands: Single Chain Fragments Provide Higher Specificity than Antibodies.” Bioconjugate Chemistry, vol. 29, no. 11, 21 Sept. 2018, pp. 3626–3637, https://doi.org/10.1021/acs.bioconjchem.8b00564.

 Li, Xin, et al. “A Versatile Method for Conjugating Lipid Nanoparticles on T Cells through Combination of Click Chemistry and Metabolic Glycoengineering.” Biotechnology Journal, vol. 19, no. 1, Jan. 2024, https://doi.org/10.1002/biot.202300339