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Ultra-Stabilization Reagent for Proteins and Antibodies Protein Hyper-Stabilizing Reagent (PEG-NH2-PRX)

Date：July 30 2026Web Page No：160186

PEG-NH2-PRX is an advanced reagent designed to recognize the specific shape of proteins and antibodies, wrapping around them to achieve reversible, non-covalent polyethylene glycol (PEG) modification on the molecular surface. Simply mixing this reagent with target proteins or antibodies dramatically enhances their stability and, depending on the protein type, significantly improves blood circulation retention.

＊The products are for research use only.

Challenges with Conventional Stabilization Methods

While the medical and pharmaceutical applications of proteins like antibodies and enzymes are rapidly expanding, their low physiological stability, short half-life in blood, and strict transport or storage requirements pose significant challenges.
Traditional approaches to improve stability include adding sugars, amino acids, or polymers, or performing chemical PEGylation. However, conventional additives often provide insufficient stabilization, while chemical covalent modification frequently impairs the intrinsic physiological activity of the protein. For instance, interferon-α and insulin are well-known to lose a major portion of their activity when chemically modified with PEG 1,2. Consequently, there is a strong demand for a method that ensures high stability without compromising biological activity.

1. Bailon, P., et al., "Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon α-2a for the treatment of hepatitis C", Bioconjugate Chem., 12(2), 195-202(2001). [PMID: 11312680]
2. Madsbad, S., LY2605541--a preferential hepato-specific insulin analogue, Diabetes, 63(2), 390-392(2014). [PMID: 24464715]


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Mechanism and Principle

The PEG-NH2-PRX reagent utilizes a polyrotaxane structure consisting of a PEG axis threaded through multiple α-cyclodextrin molecules. Each cyclodextrin molecule is further modified with PEG chains and amino groups (-NH2).
Because the cyclodextrin molecules can move and rotate freely along the PEG axis, the PEG-NH2-PRX structure dynamically deforms based on the shape and charge distribution of the target protein upon mixing. The amino groups efficiently interact with the negative charges on the protein surface, forming a stable complex that effectively coats the protein with protective PEG chains. Since this coating relies on non-covalent, reversible interactions, it preserves the full physiological activity of enzymes, insulin, and other therapeutic proteins without risk of denaturation.

Mechanism of PEG-NH2-PRX

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Features

  • Broad Applicability: Successfully forms complexes with various proteins including insulin, albumin, hyaluronidase, and antibodies. (Note: Highly basic proteins like lysozyme may struggle to form efficient complexes).
  • Simple Protocol: Achieved by simply mixing the reagent and protein in an aqueous solution. While optimal ratios vary by target, an initial test at a 1:1 molar ratio is recommended.
  • Enhanced Performance: Significantly upgrades protein stability and, in some cases, extends blood circulation time.
  • High In Vivo Safety: In vivo rat studies showed no adverse impacts on body weight, organ weight, or blood chemistry panels.
  • High Solubility: Dissolves easily in water and standard PBS buffers.

Specifications

  • Estimated Molecular Weight: > 300 kDa
  • Average alpha-cyclodextrin threading rate: 59.4 molecules per polyrotaxane molecule
  • Average amino group (-NH2) modifications: 2.04 per alpha-cyclodextrin molecule
  • Average PEG modifications: 1.58 per alpha-cyclodextrin molecule

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Reference Data

Complex Formation with Insulin

Insulin and PEG-NH2-PRX were mixed in PBS and subjected to centrifugal filtration using a 50 kDa molecular weight cut-off (MWCO) filter. The insulin concentration in the filtrate was measured to evaluate the complex formation rate, which revealed that almost all of the insulin formed a complex with PEG-NH2-PRX (left figure below). Furthermore, CD spectrum measurements demonstrated that the secondary structure of insulin remained virtually unchanged even after forming the complex with PEG-NH2-PRX (right figure below).

Complex Formation with Insulin

Sustained Hypoglycemic Effect

Insulin and PEG-NH2-PRX were mixed in PBS and subcutaneously administered to diabetic rats. The measurement results of the time-course changes in rat blood glucose levels demonstrated that the insulin–PEG-NH2-PRX complex has the effect of prolonging the glucose-lowering activity over a long period without compromising the biological activity of insulin.

Sustained Hypoglycemic Effect

Shaking and Physical Stress Stability

Shaking and Physical Stress Stability

Proteins are prone to aggregation caused by chemical and physical stress, and physical stress from shaking particularly poses a major challenge during transport. When PEG-NH2-PRX was mixed with an antibody (IgG) and shaken at 500 rpm at room temperature, the antibody alone mostly aggregated within 24 hours. In contrast, the antibody–PEG-NH2-PRX complex showed virtually no aggregation even after 7 days of continuous shaking.


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Original Article

Utatsu, K., et al., “Supramolecular polymer-based transformable material for reversible PEGylation of protein drugs.” Materials Today Bio., 12, 100160 (2021). [PMID: 34841242]


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Product Information

[Date : August 05 2026 00:08]

Detail Product Name Product Code Supplier Size Price
Protein Hyper-stabilizing Reagent (PEG-NH2-PRX)
DatasheetThis may not be the latest data sheet. 		NCS003 CYD 10 mg $966

Description It recognizes the shape of protein and antibody, wraps around them, and reversibly modifies the protein molecular surface with PEG. It improves the stability and retention of protein and antibody in blood just by mixing.
Storage RT CAS
Link

[Date : August 05 2026 00:08]

Protein Hyper-stabilizing Reagent (PEG-NH2-PRX)

DatasheetThis may not be the latest data sheet.


  • Product Code: NCS003
  • Supplier: CYD
  • Size: 10mg
  • Price: $966

Description It recognizes the shape of protein and antibody, wraps around them, and reversibly modifies the protein molecular surface with PEG. It improves the stability and retention of protein and antibody in blood just by mixing.
Storage RT CAS
Link

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