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Activated PEG

Overview of activated PEG materials

NOF has been producing a high-quality activated PEGs, SUNBRIGHT series, which possess the most suitable quality for preparation of physiologically active drug and biologics. SUNBRIGHT series are characterized as extremely high-purity PEGs with a variety of functional groups, whereby the products of this series are recognized as optimal PEGylation drugs. As illustrated in this figure, application of the activated PEGs with various functional groups enable introduction of the PEG chains into drugs, enzymes, phospholipids and other biologics. Covalent conjugation of hydrophobic macromolecules with activated PEGs leads to the formation of macromolecular micelles (Polymer Micelles), which allow homogeneous dispersion of hydrophobic drugs in aqueous media. Furthermore, when the PEGylated phospholipids are used as liposomes, the aqueous layer can be added to its surface, with homogeneous dispersal of the liposome preparations encapsulating drugs within them.

Activated PEGs
As stated above, PEGylation plays an important role in the stabilization of drugs, reduction of their antigenicity and decrease in the drug doses, besides augmenting the targeting ability via binding biologics onto their surfaces. We can do supply our activated PEGs from small scale reagent grade to huge amount GMP grade with high purity.

What is PEGylation?

PEGylation technology is applied for biologics modifications such as cytokines, antibody fragment, interleukins, hormones, oligonucleotides and some of proteins and peptides.

PEGylation can be effected to

  • Improving Bioavailability
  • Prolonging Blood Circulation
  • Maximizing Pharmacokinetics
  • Low-profiling Immunogenicity

NOF provides high-performance activated PEGs for PEGylated drugs from early development stage to commercial use with our 20 years of experience of manufacturing high-quality methoxy polyethylene glycol, which is a starting material of activated PEG for pharmaceutical area. Our activated PEGs have a narrow polydisperity and low diol content with wide range of molecular weight, from 2kDa to 80kDa.

PEG -conjugation

Analysis of PEG-ALD-Insulin by SDS-PAGE with Coomassie brilliant blue. Insulin was reacted with NOF PEG-ALD at 4°C . The PEGylated insulin was purified on Q Sepharose Fast Flowcolumn.

lane M molecular weight markers
lane 1 Insulin
lane 2 PEG(ME-050AL)-insulin eluate
lane 3 PEG(ME-100AL)-insulin eluate
lane 4 PEG(ME-200AL)-insulin eluate
lane 5 PEG(ME-300AL)-insulin eluate

Coupling of PEG derivatives to Proteins: examples of conditions

  1. Coupling of PEG-NHS derivatives to protein amines (PEG-NHS + Protein-NH 2) Conditions 1: 50 mM phosphate buffer (pH 7.2), 4℃, 6 hrs *1)
    Conditions 2: Borate-phosphate buffer (pH 8.0), 25℃, 2 hrs *2)
  2. Coupling of PEG-Aldehyde derivatives to the NH 2 group of proteins (PEG-Ald + Protein-NH 2)
    Conditions : sodium cyanoborohydride (10 eq . .), 4 deg C, 20 hrs *3)
  3. Coupling of PEG-Maleimide derivatives to the SH group of proteins (PEG-Maleimide + Protein-SH)
    Conditions: 100 mM phosphate buffer (pH 6.5), 4 deg C, 4 hrs
  4. Coupling of PEG-NH 2 derivatives to the COOH group of proteins (PEG-NH 2 + Protein-COOH)
    Conditions: 50mM phosphate buffer (pH 7.2), WSC (2 eq.), 4 deg C, 10 hrs
  5. Coupling of PEG-p-Nitrophenyloxycarbonyl derivatives to the NH 2 group of proteins (PEG-NP + Protein-NH 2)
    Conditions: borate-phosphate buffer (pH 8.0-8.3), r.t, overnight *2)
*1) Abuchowski, A., et al. (1984) Cancer Biochem. Biophys. 7, 175.
*2) Sartore, L., et al. (1991) Appl. Biochem. Biotechnol. 27, 45
*3) US 5,824,784

Functional Groups of PEG derivatives

We supply different series of PEG derivatives with various versatile functional groups.


PEG Reactive group (X*)

Target groups




-NH2, -OH, -SH



-NH2, -OH, -SH



-NH2, -OH, -SH



-NH2, -OH, -SH



-NH2, -OH, -SH



-NH2, -OH, -SH



-NH2, -OH, -SH

p-Nitrophenyl carbonate PEG



- NH2

Aldehyde PEG



- NH2



- NH2

Amine PEG







Thiol PEG



-SH, Maleimide, -COOH

Maleimide PEG








-CH2CH2CH2-NHCO- CH2CH2CH2CH2CH2-Maleimide


Iodoacetamide PEG




Aminoxy PEG




* PEG Reactive Group (X) -O-(CH2CH2O)n-X or -O-X

NHS: n-succinimidyl

Quality of Activated PEG materials

Purity of NOF’s activated products

We use our advanced technologies to measure the quality of our activated PEGs. The following are the typical analysis data for each type of activated PEGs which are measured by NMR or HPLC methods. Please note that those numbers are not specification of the product.

NHS type

CS type mPEG-succinimidyl succinate (Mw 2k and 5k) : activity over 95% (NMR)

GS type mPEG-succinimidyl glutarate (Mw 5k, 10k, 20k, 30k and 40k) : activity around 95% (NMR)

AS type mPEG-succinimidyl methyl ester (Mw 2k and 5k) : activity around 95% (NMR)

HS type mPEG-succinimidyl pentyl ester(Mw 5k, 10k, 20k, 30k and 40k): activity around 95% (NMR)

TS type mPEG-succinimidyl carbonate(Mw 5k, 10k, 12k, 20k, 30k and 40k): activity over 95% (HPLC)

pNP type (NP series)

mPEG-p-nitrophenyl (Mw 2k, 5k, 10k, 20k, 30k and 40k): activity over 95% (HPLC)

Aldehyde type(AL series)

mPEG-propylaldehyde (Mw 5k, 10k, 20k, 30k and 40k): activity over 85% (HPLC). The activity for Mw20k, it is over 92% as actual data by HPLC.

Amine type

PA type mPEG-propylamine (Mw 2k, 5k, 10k, 12k, 20k, 30k and 40k): activity over 95% (HPLC)

EA type mPEG-ethylamine (Mw 5k, 10k, 20k, 30k and 40k): activity over 95% (HPLC)

thiol type(SH series)

mPEG-thiol (Mw 2k, 5k, 10k, 20k, 30k and 40k): activity around 95% (HPLC)

Maleimide type(MA series)

mPEG-maleimide (Mw 2k, 5k, 10k, 20k, 30k and 40k): activity around 95% (HPLC)

Oxyamine type(CA series)

mPEG-oxyamine (Mw 10k, 20k, 30k and 40k): activity around 95% (HPLC)

Iodoacetoamide type(IA series)

mPEG-irdoacetoamide (Mw 20k, 30k and 40k): activity around 90% (HPLC)

Analytical Technology for PEG reagents

NOF has more than 20 years history for manufacturing of high-quality mPEGs and Activated PEGs. These experiences enable NOF to have thorough knowledge of PEGs and considerable achievement in analysis of Activated PEGs. We also have invented innovative analytical methods for assaying purity of activated PEGs and for determining impurity levels. (*Patent No.: JP4543917) Previously, the activity for activated PEGs is measured by NMR. However, this method is not very good detection due to polymer, especially for high molecular weight. We developed the analysis method by using HPLC. As the result of the analysis, the activity sometime seems lower than the result of NMR because main peak can completely separate from non-active peak and activated impurity peaks (like dimer).

HPLC analysis for M-PEG-COOH


GPC Analysis of M-PEG5K and M-PEG-30K

GPC Analysis of M-PEG5K and M-PEG-30K

MALDI-TOF-MS Analysis of M-PEG5K and M-PEG-30K

MALDI-TOF-MS Analysis of M-PEG5K and M-PEG-30K

GMP Supply of Activated PEG materials

cGMP Manufacturing Facilities

NOF Activated PEGs, SUNBRIGHT® series are produced in facilities with state-of-the-art technology, operated under cGMP. The cGMP facilities are capable of producing small to large batch sizes, using proprietary know-how on scale-up procedure, depending on customers' needs. These cGMP facilities have been audited by pharmaceutical companies throughout the world. NOF receives high reputation from our customers.

cGMP Manufacturing Facilities

Research & Development

Our R&D facility was opened in December 2005. This allows us to continue our development of novel activated PEGs and technologies for PEGylation.

Custom Manufacturing of Activated PEG materials

NOF has over 20 years of experience in supplying high-quality methoxy polyethylene glycol (mPEG) for pharmaceutical market. The mPEG is starting material of PEG derivatives, which are patented through our proprietary technology. Based on extensive range of technological know-how and capabilities, NOF offers custom manufacturing of Activated PEGs from early stage development to commercial scale. Sizewise, we can offer gram size synthesis to kg size for non GMP product. We also offer cGMP custom synsthesis.

Customized PEGylation Services

From early development to commercial production

PEGylation has been an established technology for decades and successful in making the top ten marketed PEG-drugs several billion dollars sales in 2106. Nevertheless, the development of PEGylated drug is challenging and requires extensive experience in both chemistry and biochemistry. Only a few companies worldwide have sufficient know-how and resources to successfully perform such development on their own.

NOF and Celares GmbH offer customized PEGylation services from early development through clinical, up to commercial stage on fee-for-service basis. By utilizing this service, customers obtain access to the required development facility and benefit from:

  • More than 20 years of experience in the development of PEGylated drugs
  • Combined experience in chemistry and biologics
  • Increased speed of their PEGylation development
  • Minimizing the risk of failure in PEGylation
  • Saving own resources for API development
  • Continued consistent supply of highly pure activated PEG products from research through clinical development and commercial stage

Customers may select between single service modules according to their individual needs or complete development package. A complete development project comprise five steps (feasibility study, process development, development analytical methods, stability studies, and production) and takes 12-18 months from early screening to clinical GMP-production.

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