Activated PEGs for N-terminal PEGylation

JenKem Beijing R&DJenKem Technology provides high quality PEG aldehyde derivatives for N-terminal PEGylation with high purity and low polydispersity.

JenKem Technology’s activated PEG aldehydes for N-terminal PEGylation are reactive towards the N-terminal amines taking advantage of the lower pKa of the N-terminal amine in proteins. 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 aldehyde group, may help to reduce the number of attachment sites to a protein molecule. Y-shaped Propionaldehyde PEG is reactive towards N-terminal amines in the presence of a reducing reagent at pH 5-8; less selective but more reactive compared with Y-AALD-40K. Y-shaped Acetaldehyde PEG is an N-terminal amine reactive PEG in the presence of a reducing reagent at pH 5-8; less reactive but more selective compared to linear PEG aldehydes. Methoxy PEG Propionaldehyde is an N-terminal amine reactive PEG that reacts at pH 5-8 in the presence of a reducing reagent; methoxy PEG Propionaldehyde with MW 20kDa, M-ALD-20K, is a PEG raw material for biosimilars of Peg-filgastrim, Peg-GSF, PEG-rhGCSF, or Neulasta® [12].

N-Terminal PEGylation products 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 N-Terminal PEGylation products. For global distribution, please visit link. To order directly from JenKem Technology:

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Y-shape Aldehyde PEGs
PEG PRODUCT SUBSTITUTION REACTIVITY DETAILS
Y-PEG-AALD ≥ 95% Y-shaped PEG Acetaldehyde reacts with N-terminal amines in the presence of a reducing reagent at pH 5-8. Y-shape PEG Acetaldehyde is more selective but less reactive compared with Y-shaped Propionaldehyde.[1,2]
Y-PEG-PALD ≥ 95% Y-shaped PEG Propionaldehyde reacts with N-terminal amines in the presence of a reducing reagent at pH 5-8. Y-shape PEG Propionaldehyde is less selective but more reactive compared with Y-shaped Acetaldehyde.[1-4]
Linear Methoxy Aldehyde PEGs
PEG PRODUCT SUBSTITUTION REACTIVITY DETAILS
M-PEG-ALD ≥ 95% Methoxy PEG Aldehyde reacts with N-terminal amines, such as the N-terminal on proteins for Peg-filgastrim Peg-gsf, PEG-rhGCSF, Neulasta®, and related biosimilars, at pH 5-8 in the presence of a reducing reagent. [5-11, 13-20]. Methoxy Propionaldehyde PEG with MW 20000 (M-ALD-20K) is employed as a PEG raw material for pegfilgrastim PEGylated biosimilars [12].
Heterobifunctional PEGs Functionalized with Propionaldehyde
Heterobifunctional Aldehyde PEGs

References:

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

2. Farkas, T, et al., Additional Studies in the Separation of PEGylated Proteins by Reversed Phase Chromatography, LC/GC. 2008.

3. Liebner, R., et al., Head to Head Comparison of the Formulation and Stability of Concentrated Solutions of HESylated versus PEGylated Anakinra, Journal of Pharmaceutical Sciences 2015, 104(2): 515-526.

4. 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.

5. Zhang, L., et al., Suppression for lung metastasis by depletion of collagen I and lysyl oxidase via losartan assisted with paclitaxel-loaded pH-sensitive liposomes in breast cancer, Drug Delivery, 2016.

6. Mayolo-Deloisa, K., et al., APEGylated protein separation using different hydrophobic interaction supports: Conventional and monolithic supports. Biotechnology progress. 2016.

7. Zhang, Y., et al., Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer. Scientific Reports. 2016; 6:21225.

8. Abbasi, S., et al., Design and cell cytotoxicity assessment of palmitoylated polyethylene glycol-grafted chitosan as nanomicelle carrier for paclitaxel. J. Appl. Polym. Sci., 2015, 133, 43233.

9. Wu, L., et al., N-Terminal Modification with Pseudo-Bifunctional PEG-Hexadecane Markedly Improves the Pharmacological Profile of Human Growth Hormone, Molecular Pharmaceutics, 2015, DOI: 10.1021/mp500680p.

10. Zhang, L., et al., High Tumor Penetration of Paclitaxel Loaded pH Sensitive Cleavable Liposomes by Depletion of Tumor Collagen I in Breast Cancer, ACS Applied Materials & Interfaces, 2015.

11. Mata-Gómez, M. A.,et al., Dielectrophoretic behavior of PEGylated RNase A inside a microchannel with diamond-shaped insulating posts. Electrophoresis, 2015.

12. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000420/WC500025941.pdf.

13. Tiwari, D., et al., Efficient Purification of rhG-CSF and its PEGylated Forms and Evaluation for In Vitro Activities, Protein and Peptide Letters, 2015, Volume 22, Number 10, pp. 877-884(8).

14. Schulz, J. D., Site-Specific Polymer Conjugation Stabilizes Therapeutic Enzymes in the Gastrointestinal Tract. Adv. Mater., 2015, doi:10.1002/adma.201504797.

15. Wu, L., Phenyl Amide Linker Improves the Pharmacokinetics and Pharmacodynamics of N-Terminally Mono-PEGylated Human Growth Hormone, Mol. Pharmaceutics, 2014, 11(9), p: 3080–3089.

16. Xue, X., et al., Heat treatment increases the bioactivity of C-terminally PEGylated staphylokinase. Process Biochemistry, 2014. 49(7): p. 1092-1096.

17. Pink, A., et al., Purification, characterization and plasma half-life of PEGylated soluble recombinant non-HA-binding CD44, BioDrugs, 2014, 28(4) p:393-402.

18. 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.

19. Li, R., et al., Preparation and Characterization of Biological Non-toxic Hybrid Nanoparticles Based on Lactide and Poly(ethylene glycol) Loading Docetaxel for Anticancer Drug Delivery, Chinese Journal of Chemical Engineering, 2014, Volume 22, Issues 11–12, Pages 1357-1362.

20. Mejia‐Manzano, L.A., et al., Optimized purification of mono‐PEGylated lysozyme by Heparin Affinity Chromatography using Response Surface Methodology, Journal of Chemical Technology and Biotechnology, 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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