JenKem Technology provides high quality activated Y-shaped PEG derivatives with high purity and low polydispersity.

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 NHS group, may help to reduce the number of attachment sites to a protein molecule. Y-shape PEG NHS ester is readily dissolved in aqueous buffers and enables simple and efficient modification of proteins and other biological agents that contain lysines. JenKem proprietary Y-shape PEGs have been employed in PEGylation of nanoparticles, Cp40, aptamers, G-CSF, Gentamicin, IFN-α2a, IFN-α2b, LIF receptor antagonist (LA), L-RNA, rhGH, and TNF-α, and others.

JenKem Technology provides Y-shape branched PEG derivatives for amine pegylation (Y-NHS-40K, Y-COOH-40K), thiol pegylation (Y-MAL-40K), N-terminal PEGylation (Y-AALD-40K and Y-PALD-40K), C-terminal PEGylation (Y-NH2-40K), click chemistry (Y-ALKYNE-40K), and other applications (such as Y-FITC-40K). Y-shape PEG derivatives are chemically purified during synthesis and are essentially free of activated bifunctional PEG side products.

Y-NHS-40k PEGylation

Schematic of Amine PEGylation of Proteins with Y-PEG-NHS

JenKem Technology Y-Shaped PEGs with molecular weights 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.

JenKem Technology provides GMP grade PEG derivatives and bulk orders via custom synthesis, offering the opportunity to match customers’ special quality requirements. JenKem Technology is capable of development and synthesis of a wide range of GMP PEG derivatives starting at 200g up to 40 kg or greater batches, under ISO 9001 and ISO 13485 certified quality management system, following ICH Q7A guidelines. For inquiries on cGMP production of PEG derivatives and related PEGylation services please contact us at tech@jenkemusa.com.

For global distribution, please visit link. To order directly from JenKem Technology:

PEG PRODUCT SUBSTITUTION REACTIVITY DETAILS
≥95% Y-shaped NHS PEG ester. Reactive towards the amino group of lysine(s) on proteins or other biologics. Amine PEGylation with Y-shape PEG NHS can be completed in less than 1hr at pH 7-8. [1-3]
≥95% Y-shaped PEG Carboxyl  Stable PEG intermediate for amine PEGylation
≥95% Y-shaped  PEG Maleimide. Thiol reactive PEG [4-6] ; reacts at pH 5.0-6.5
≥95% Y-shaped PEG Acetaldehyde. N-terminal amine reactive PEG in the presence of a reducing reagent; less reactive but more selective compared to linear PEG aldehydes; reacts at pH 5-8. [7, 8]
≥95% Y-shaped  PEG Propionaldehyde. Reactive PEG for N-terminal amine in the presence of a reducing reagent; less selective but more reactive compared with Y-AALD-40K; reacts at pH 5-8. [7-10]
≥95% Y-shaped PEG Amine, more reactive towards acylating agents than the hydroxyl group; readily undergoes reductive amination reactions [11-12]
≥90% Y-shape PEG Fluorescein, suitable for fluorescence monitoring of the PEGylation reaction with Y-shaped PEGs
≥95% Y-shaped PEG Alkyne is a high quality click PEG reagent for reaction with azide groups
U-shaped PEG Derivatives
PEG PRODUCT SUBSTITUTION REACTIVITY DETAILS
≥ 95% MPEG2 Lysine NHS Ester is reactive towards the amino group of lysine(s), or present on the active ingredients of peginterferon alpha-2a, Macugen® PEG-aptamer, or Pegasys®
≥ 95% MPEG2 Lysine Maleimide  with superior quality; reacts with thiol groups on cystein side chains, such as thiols on the active ingredient of Certolizumab- pegol (Cimzia®).
Applications of Y-Shape PEGs
Y-shape PEGs for Drug Delivery and Diagnostics Drug Molecule or Other Entity PEGylated with Y-shape PEG References
Y-shape PEG Amine Paclitaxel [11]
Y-shape PEG Maleimide siRNA [4]
Cocaine esterase [14, [6]
Y-shape PEG NHS Calcium phosphate nanoparticles [15]
Cp40 [16]
DNA aptamer (SOMAmer) [2]
G-CSF [17]
Gentamicin [18]
IFN-α2a [19]
IFN-α2b [20]
LIF receptor antagonist (LA) [21]
RNA aptamer [27]
L-RNA (Spiegelmer) [13], [22], [23]
rhGH [24]
TNF-α [25], [26]
Y-shape PEG Propionaldehyde Laccase [10]
Ubiquitin-derived 77405 protein [7]
References

1. Guo, L., et al., Application Instructions for Y-NHS-40K for Amine PEGylation, link.

2. AlQahtani, A.D., et al., Production of “biobetter” glucarpidase variants to improve drug detoxification and antibody directed enzyme prodrug therapy for cancer treatment, European Journal of Pharmaceutical Sciences, 2019, V. 127, P. 79-91.

3. Winship, A.L., Interleukin-11 alters placentation and causes preeclampsia features in mice, Proc Natl Acad Sci U S A., 2015, 112(52):15928-33.

4. Li, H., et al., Dual MMP7-Proximity-Activated and Folate Receptor-Targeted Nanoparticles for siRNA Delivery, Biomacromolecules, 2015, 16 (1), p: 192–201.

5.  Yu, W., et al., PEGylated recombinant human interferon-ω as a long-acting antiviral agent: Structure, antiviral activity and pharmacokinetics. Antiviral Research, 2014, 108: p. 142-147.

6. Fang, L., et al., Rational design, preparation, and characterization of a therapeutic enzyme mutant with improved stability and function for cocaine detoxification. ACS chemical biology, 2014, 9(8):1764-72.

7. Lorey, S., et al, Novel Ubiquitin-derived High Affinity Binding Proteins with Tumor Targeting Properties, The Journal of Biological Chemistry, 2014, 289,8493-8507.

8. Yu, K.-M., et al., Preclinical evaluation of the mono-PEGylated recombinant human interleukin-11 in cynomolgus monkeys, Toxicology and Applied Pharmacology, 2018, V. 342, P. 39-49.

9. Yu, K.-M., et al., Pharmacokinetic and Pharmacodynamic Evaluation of Different PEGylated Human Interleukin-11 Preparations in Animal Models, Journal of Pharmaceutical Sciences, 2018.

10. Mayolo-Deloisa, K., et al., Aldehyde PEGylation of laccase from Trametes versicolor in route to increase its stability: effect on enzymatic activity, Journal of Molecular Recognition, 2015, 28(3): 173-179.

11. 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.

12. Hoehlig, K., et al., A novel C5a-neutralizing mirror-image (l-)aptamer prevents organ failure and improves survival in experimental sepsis. Mol Ther, 2013, 21(12): p. 2236-46.

13. Hoffmann, S., et al.,  RNA Aptamers and Spiegelmers: Synthesis, Purification, and Post-Synthetic PEG Conjugation. Current Protocols in Nucleic Acid Chemistry, 2011, 46:4.

14. Narasimhan, D., et al., Subunit Stabilization and Polyethylene Glycolation of CocaineEsterase Improves In Vivo Residence Time. Mol Pharmacol, 2011, 80, 1056.

15. Ashokan, A., et al., Multifunctional calcium phosphate nano-contrast agent for combined nuclear, magnetic and near-infrared in vivo imaging. Biomaterials, 2013, 34, 7143.

16. Risitano, A.M. ,et al., Peptide inhibitors of C3 activation as a novel strategy of complement inhibitionfor the treatment of paroxysmal nocturnal hemoglobinuria, Blood, 2014, 123, 2094.

17. Wang, S., et al.,Y-type polyethylene glycol modified G-CSF and preparation method and use thereof. Patent CN200780051378, 2007.

18. Marcus, Y., et al., Turning Low-Molecular-Weight Drugs into Prolonged Acting Prodrugs by Reversible PEGylation: A Study with Gentamicin. J Med Chem, 2008, 51, 4300.

19. Zhou, W., et al., Interferon alpha 2a modified by polyethylene glycol, its synthesis process and application. Patent CN200780050541, 2007.

20. Zhou, W., et al., Interferon alpha 2b modified by polyethylene glycol, its synthesis process and application. Patent CN200780050542, 2007.

21. Menkhorst, E., et al., Vaginally Administered PEGylated LIF Antagonist Blocked Embryo Implantation and Eliminated Non-Target Effects on Bone in Mice. PLoS ONE, 2011, 6, e19665.

22. Roccaro, A.M. et al. SDF-1 Inhibition Targets the Bone Marrow Niche for Cancer Therapy. Cell Reports, 2014, 9, 118.

23. Khan, M.A., et al., Targeting complement component 5a promotes vascular integrity and limits airway remodeling. PNAS, 2013, 110, 6061.

24. Zhou, W., et al., Double-stranded polyethylene glycol modified growth hormone, preparation method and application thereof. Patent CN200880009718, 2008.

25. ChuanYun, D., et al., Linkage with cathepsin B-sensitive dipeptide promotes the in vitro and in vivo anticancer activity of PEGylated tumor necrosisfactor-alpha (TNF-α) against murine fibrosarcoma. Sci China Life Sci, 2011, 55, 128.

26. ChuanYun, D., et al., Preparation and evaluation of a new releasable PEGylated tumor necrosis factor-α(TNF-α) conjugate for therapeutic application. Sci China Life Sci, 2013, 56, 51.

27. Haruta, K., et al., A Novel PEGylation Method for Improving the Pharmacokinetic Properties of Anti-Interleukin-17A RNA Aptamers, Nucleic acid therapeutics, 2017, 27(1):36-44.

Founded in 2001 by 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 in-house polymerization from ethylene oxide, enabling facile traceability for 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.