Polypeptide and protein drugs refer to polypeptide and protein biopharmaceuticals for prevention, treatment, and diagnosis. Polypeptides are compounds in which alpha-amino acids are linked together by peptide chains, which are also intermediates in protein hydrolysis. The N polypeptide chain is entangled in a certain spatial structure to form a protein. In contrast, macromolecular proteins also produce polypeptides upon hydrolysis. Although the overall trend of these drugs is "humanized", these drugs are still immunogenic in the clinical setting and require scientists to explore. Creative Biolabs has a rich background in protein drug immunogenicity, a top design team and a high-quality technology platform to help you reduce clinical adverse reactions.
Peptide and protein biopharmaceuticals can be classified into amino acids and their derivatives, peptides and protein drugs, enzymes and coenzymes, nucleic acids and their degradants and derivatives, and carbohydrates, lipid drugs, cell growth factors and biologic drugs.
Clinically, therapeutic proteins have been shown to activate immune cells in the body, causing an immune response, and a large number of antibodies continue to be produced. Such conditions can easily cause adverse reactions and toxic side effects of the body. Despite the convenience of routine animal model testing, it is difficult to deduce the immunogenicity of the drug in humans. Therefore, further research is needed for the detection and removal of immunogenicity.
The key amino acids in T cells are identified and substituted by computer calculations which are often responsible for stimulating the immune response. More importantly, the effects of this substitution on protein structure can also be assessed using computer simulations. Besides, structural modifications can be made to major histocompatibility complex (MHC) alleles to inhibit activated T cells.
The polyethylene glycol modifier is a polyethylene glycol with a functional group, also called modified polyethylene glycol, a modified PEG that currently was used for protein and peptide drug modification to increase the half-life in vivo, reduce immunogenicity, and also increase the water solubility of the drug. PEGylation can increase protein solubility and fluid dynamics, which promotes therapeutic proteins to evade kidney metabolism and prolong circulation time in the body.
Fig.1 Stimulation of T helper (Th) cells by antigens. (Weber, 2009)
Creative Biolabs provides a variety of peptide and protein drug de-immunization services to reduce immunogenicity and adverse reactions. If you are interested in our de-immunization services, please contact us and we will provide you with technical support and services as soon as possible.
Other optional RDIT® de-immunization services:
De-immunization of peptide and protein drugs involves modifying these molecules to reduce their immunogenicity—essentially their potential to provoke an immune response. This process is crucial for ensuring that therapeutic proteins are tolerated by the patient's immune system, thereby enhancing their efficacy and safety.
Many protein therapeutics are derived from non-human sources or are recombinant forms that can be recognized as foreign by the human immune system. De-immunization minimizes this recognition, preventing immune reactions that can neutralize the therapeutic effects of the drug and cause adverse health effects.
Techniques include altering the amino acid sequence to remove T-cell epitopes, glycosylation to shield potential immunogenic sites, and fusion to human serum proteins. Advanced methods like computational epitope prediction and molecular engineering are also used to redesign proteins for reduced immunogenicity.
While the primary goal is to reduce immunogenicity, it is critical that these modifications do not adversely affect the biological activity or stability of the protein. Careful design and extensive testing are essential to ensure that therapeutic efficacy remains intact.
The success of de-immunization is measured by a combination of laboratory assays and clinical evaluations. This includes testing for reduced antibody formation in response to the drug, maintaining therapeutic activity, and monitoring patients for adverse immune reactions during clinical trials.
Computational tools are crucial for predicting immunogenic epitopes and simulating how amino acid changes could affect a protein's structure and function. These tools help streamline the de-immunization process by identifying potential targets for modification before experimental testing.
Use the resources in our library to help you understand your options and make critical decisions for your study.
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