Activated PEGs for C-Terminal PEGylation

RnD JenKemJenKem Technology provides high quality polyethylene glycol (PEG) derivatives for C-terminal PEGylation with high purity and low polydispersity, from non-GMP laboratory scale, to large commercial scale in GMP and non-GMP grade.

Amine functionalized PEGs are the most utilized PEG reagents for C-terminus PEGylation proteins and peptides. PEGylation of carboxyl groups with PEG amines requires the presence of coupling agents, such as water-soluble EDC, with or without NHS, for aqueous PEGylation at pH 7.2 [1-4]; or water-insoluble DCC, for non-aqueous carboxyl PEGylation reactions [5].

JenKem Technology manufactures linear and branched multi-arm amine functionalized PEGs, either homofunctional and heterobifunctional. The sterically bulky structure of JenKem Technology’s proprietary Y-shape branched PEG derivatives, consisting of two linear methoxy PEG chains attached to a central core with an active amine group, may help to reduce the number of attachment sites to a protein molecule.

Activated PEG products for C-terminal PEGylation with molecular weights, branching, and functional groups not listed in our online catalog may be available by custom synthesis. Please inquire at tech@jenkemusa.com about pricing and availability of custom PEGs for Carboxyl PEGylation. For global distribution, please visit link. To order directly from JenKem Technology:

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Y-shape PEG Amine
PEG PRODUCT SUBSTITUTION REACTIVITY DETAILS
Y-NH2-40K ≥ 95% Y-shape PEG Amine, more reactive towards acylating agents than the hydroxyl group; readily undergoes reductive amination reactions. JenKem proprietary Y-shape PEGs are more selective, due to their sterically bulky structure. [6]
Methoxy PEG Amine
PEG PRODUCT SUBSTITUTION REACTIVITY DETAILS
M-PEG-NH2 ≥ 95% Methoxy PEG Amine. Attaches via stable linkages, such as amide, urethane, urea, secondary amine; the HCl salt form provides stability for the solid form of M-PEG-NH2 [7, 19, 22-26]
Methoxy-PEG5-AmineMethoxy-PEG6-Amine ≥ 95% Monodisperse Methoxy PEG5 Amine and Methoxy PEG6 Amine. Attaches via stable linkages, such as amide, urethane, urea, secondary amine. JenKem Technology’s monodisperse PEG products are produced via very reproducible chemical reactions and lack the polydispersity of traditional PEG polymers.
Homobifunctional Amine PEGs
PEG PRODUCT SUBSTITUTION REACTIVITY DETAILS
NH2-PEG-NH2 ≥ 95% Amine PEG Amine (PEG diamine). PEG Crosslinker, attaches via stable linkages, such as amide, urethane, urea, secondary amines. [8-18]
Amine-PEG8 -AmineAmine-PEG12 -Amine ≥ 95% Monodisperse Amine PEG8 Amine or Amine PEG12 Amine (Discrete PEG bisamine). PEG Crosslinker, attaches via stable linkages, such as amide, urethane, urea, secondary amines. JenKem Technology’s monodisperse PEG products are produced via very reproducible chemical reactions and lack the polydispersity of traditional PEG polymers. [20, 21]
Heterobifunctional Amine Functionalized PEGs:

Heterobifunctional PEGs Functionalized with Protected Amine
Heterobifunctional PEGs Functionalized with Amine

Multiarm Homofunctional PEGs Functionalized with Amine:
Multiarm Homofunctional PEGs
Multiarm Heterobifunctional PEGs Functionalized with Amine and Protected Amine:
Multiarm Heterobifunctional PEGs

References:

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  2. Gyudo Lee, Real-Time Quantitative Monitoring of Specific Peptide Cleavage by a Proteinase for Cancer Diagnosis, Angew. Chem. Int. Ed. 2012, 51, 5837 –5841
  3. Zhang, Ti, et al., In vivo photoacoustic imaging of breast cancer tumor with HER2-targeted nanodiamonds, Proc Soc Photo Opt Instrum Eng. 2013; 8815
  4. Lin Dai, Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer, Scientific Reports 2014, 4 : 5871
  5. York, A.W., Kinetically Assembled Nanoparticles of Bioactive Macromolecules Exhibit Enhanced Stability and Cell-Targeted Biological Efficacy, Adv. Mater. 2012, 24: 733–739. DOI: 10.1002/adma.201103348
  6. Amoozgar, Z., et al., Dual-layer surface coating of PLGA-based nanoparticles provides slow-release drug delivery to achieve metronomic therapy in a paclitaxel-resistant murine ovarian cancer model, Biomacromolecules. 2014. 15(11):4187-94.
  7. Chen, G., et al., Tumor-targeted pH/redox dual-sensitive unimolecular nanoparticles for efficient siRNA delivery. Journal of Controlled Release. 2017.
  8.  Bai, J., et al., Triple-Modal Imaging of Magnetically-Targeted Nanocapsules in Solid Tumours In Vivo, Theranostics, 2016, 6(3):342-356.
  9.  Jain, S., et al., Estradiol functionalized multi-walled carbon nanotubes as renovated strategy for efficient gene delivery, RSC Advances, 2016; 6(13):10792-801
  10. Mou, J., et al., A New Green Titania with Enhanced NIR Absorption for Mitochondria-Targeted Cancer Therapy, Theranostics, 2017; 7(6):1531-1542.
  11. Chen, N., et al., Cy5.5 conjugated MnO nanoparticles for magnetic resonance/near-infrared fluorescence dual-modal imaging of brain gliomas, Journal of Colloid and Interface Science, 2015, Volume 457, Pages 27-34.
  12. Liu, S., et al., Meter-long multiblock copolymer microfibers via interfacial bioorthogonal polymerization, Adv. Mater., 2015,  DOI: 10.1002/adma.201500360.
  13. Zhang, T., et al., Targeted nanodiamonds as phenotype-specific photoacoustic contrast agents for breast cancer, Nanomedicine 2015, Vol. 10, No. 4 , Pages 573-587.
  14. Cheng, L., et al., Construction and evaluation of PAMAM–DOX conjugates with superior tumor recognition and intracellular acid-triggered drug release properties, Colloids and Surfaces B: Biointerfaces, 2015, Volume 136, Pages 37-45.
  15. Li, S., et al., Targeted imaging of brain gliomas using multifunctional Fe3O4/MnO nanoparticles, RSC Adv., 2015, 5, 33639-33645.
  16. Chen, W., et al., Assembly of Fe3O4 nanoparticles on PEG-functionalized graphene oxide for efficient magnetic imaging and drug delivery, RSC Adv., 2015, 5, 69307-69311.
  17. Rubio, N., et al., Solvent-Free Click-Mechanochemistry for the Preparation of Cancer Cell Targeting Graphene Oxide, ACS Applied Materials & Interfaces, 2015, 7 (34), 18920-18923.
  18. Chen, H., et al., A graphene quantum dot-based FRET system for nuclear-targeted and real-time monitoring of drug delivery, Nanoscale, 2015, 7, 15477-15486.
  19. Balasso, A., et al., Re-programming pullulan for targeting and controlled release of doxorubicin to the hepatocellular carcinoma cells, European Journal of Pharmaceutical Sciences, 2017.
  20. El-Gogary, R.I., et al., Polyethylene Glycol Conjugated Polymeric Nanocapsules for Targeted Delivery of Quercetin to Folate-Expressing Cancer Cells in Vitro and in Vivo. ACS Nano, 2014. 8(2): p. 1384-1401.
  21. Zhou, J., et al., In vivo evaluation of medical device-associated inflammation using a macrophage-specific positron emission tomography (PET) imaging probe. Bioorganic & Medicinal Chemistry Letters, 2013. 23(7): p. 2044-2047.
  22. Jalalvandi, E., et al., Schiff-base based hydrogels as degradable platforms for hydrophobic drug delivery, European Polymer Journal, 2017, 90:13-24.
  23. Etienne, G., et al., Influence of Fluorinated Surfactant Composition on the Stability of Emulsion Drops, Macromolecular Chemistry and Physics, 2017, 218(2).
  24. Clawson, G.A., et al., A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma, Nucleic acid therapeutics, 2017, 27(1):23-35.
  25. Giraldo, J.A., et al., The impact of cell surface PEGylation and short-course immunotherapy on islet graft survival in an allogeneic murine model, Acta Biomaterialia, 2017, 49:272-83.
  26. Yang, Q., Pretargeting with bispecific fusion proteins facilitates delivery of nanoparticles to tumor cells with distinct surface antigens, Journal of Controlled Release, 2017.

Founded in 2001 by recognized experts in PEG synthesis and PEGylation, JenKem Technology specializes exclusively in the development and manufacturing of high quality polyethylene glycol (PEG) products and derivatives, and related custom synthesis and PEGylation services. JenKem Technology is ISO 9001 and ISO 13485 certified, and adheres to ICH Q7A guidelines for GMP manufacture. The production of JenKem® PEGs is back-integrated to on-site manufacturing from ethylene oxide, enabling facile traceability for GMP regulated customers. JenKem Technology caters to the PEGylation needs of the pharmaceutical, biotechnology, medical device and diagnostics, and emerging chemical specialty markets, from laboratory scale through large commercial scale.

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