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PEGylation of Antibodies

PEGylation of Antibody

The covalent attachment of polyethylene glycol (PEG) to various proteins to modify their function has been reported over the years. A class of proteins that have recently been used in this technique are antibodies and antibody fragments. PEG is mainly used to reduce the immunogenicity of antibodies and increase the circulating half-life of antibodies. It may also have beneficial effects on the use of antibodies in certain clinical settings, such as tumor targeting. BOC Sciences is committed to providing PEGylation services of antibodies with different structures, chain lengths and linker chemistries to meet the needs of various new therapeutic entities.

Advantages of Antibody PEGylation

Currently, techniques for site-specific attachment of PEG to antibody fragments are well established. The known properties of PEG to increase plasma half-life and accumulate in tumors have led to increased application of PEGylated antibody fragments such as Fab' and scFv. This has opened up immunotherapy for chronic diseases and improved antibody targeting of tumors. Several studies on pegylated antibodies or antibody fragments in the field of oncology have shown that the biodistribution of antibodies or antibody fragments is altered after pegylation, resulting in more accumulation in tumors but not in normal tissues. This is obviously advantageous for tumor-targeted therapy when these antibodies are used to deliver cytotoxic drugs or radioisotopes. It has also been found in animal models and patients that antibody fragments may be more advantageous for tumor targeting over intact IgG due to increased tumor penetration. Thus, PEGylation has in some cases been used to overcome immune responses against antibodies or against molecules conjugated to antibodies such as bacterially derived drugs or enzymes.

PEGylation of Antibody

Benefits of PEGylation

  • Reduced antigenicity and immunogenicity of molecules linked to PEG.
  • Significant improvement in in vivo circulating half-life due to evasion of renal clearance by the polymer increasing the apparent size of the molecule above the glomerular filtration limit, and/or evasion through cellular clearance mechanisms.
  • Improve solubility. PEG has been found to be soluble in many different solvents, from water to many organic solvents such as toluene, methylene chloride, ethanol and acetone. One application of this is the use of PEG-modified antibodies, for example, for phase separation of target molecules or cells.
  • Enhance the proteolytic resistance of the binding protein.
  • Increased bioavailability by reducing losses at the subcutaneous injection site.
  • Reduced toxicity. For agents whose toxicity is related to peak plasma levels, it would be advantageous to obtain a flatter pharmacokinetic profile by subcutaneous administration of pegylated proteins. Proteins that elicit immune responses with toxic consequences may also benefit from PEGylation.
  • Improved thermal and mechanical stability of PEGylated molecules.
  • Improved formulation of materials for some sustained release (depot) dosing strategies.

Our Antibody PEGylation Capabilities

PEGylation of Antibody

In each antibody variable chain, there are three regions called complementarity determining regions or CDRs. The pocket formed by them enables the antibody molecule to bind the antigen. When these proteins are pegylated, it is very important to maintain the affinity between antibodies and antigens. One of the most common methods of attaching PEG to proteins is through amine reactions, such as the N-hydroxysuccinimide ester functional group at the end of the PEG molecule. They react with lysine residues and potentially N-terminal residues in target proteins. This approach results in the attachment of PEG to many different sites on any given protein. The number of PEG molecules attached to different protein molecules is inevitably different, that is, the degree of PEG modification is different.

With years of PEGylation experience and technological innovation, BOC Sciences has developed PEG conjugation strategies with antibody fragments of various sizes. Our PEGylated antibody services not only cover various molecular weights, but also PEGs modified with various functional groups. Our PEGylated antibody conjugation capabilities include:

AcrylateBiotinDSPEMaleimide
AldehydeBocFITCNorbornene
AlkyneCarboxylic AcidHalideSilane
AminoCholesterolHydrazideThiol
AzideDBCOHydroxylSulfonate

Reference

  1. Chapman, A.P. PEGylated antibodies and antibody fragments for improved therapy: a review. Advanced Drug Delivery Reviews. 2002, 54: 531-545.

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BOC Sciences supplies a unique variety of PEG derivatives and functional PEG polymers. Our products offer the most diverse collection of reactivity, ready-to-use functionality, and molecular weight options that you will not find anywhere else.

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PEGylation of Peptides and Proteins

PEGylation of Peptides
and Proteins

Reduce the Immunogenicity of Peptide/Protein Drugs

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APPLICATIONS

PEG linkers For Drug

Improved Circulation Half-Life

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