Peptide Modification for Drug Development
* Please kindly note that our products and services can only be used to support research purposes (Not for clinical use).
Online Inquiry
As an important part of drug development, peptide modification has a wide range of modifications and applications. This article will discuss the application of peptide modifications in anticancer, drug delivery, antimicrobial, and multivalent vaccine development, and give relevant examples.
Peptide-modified gold nanoclusters improve anti-tumor efficacy
Peptide-modified gold nanoclusters, such as GSH and TAT modifications, combine the targeting of peptides with the physicochemical properties of gold nanoclusters to significantly enhance their efficacy in cancer therapy. Under this modification, gold nanoclusters can not only stabilize the structure of the peptide but also use the targeted properties of the peptide to precisely find and enter cancer cells. For example, the peptide GSH-modified gold nanoclusters not only enhance their stability in vivo through the strong binding of sulfhydryl groups to gold but also exhibit excellent biocompatibility and antioxidant capacity, which plays an important role in anti-oxidative stress. At the same time, TAT-modified gold nanoclusters are able to more efficiently cross the cell membrane and enter the tumor cells by taking advantage of their strong cell penetration ability. In photodynamic therapy (PDT), the application of gold nanoclusters further enhances the therapeutic effect. Tumor tissues typically present high levels of hydrogen peroxide (H2O2), a property that is exploited by peptide-modified gold nanoclusters to catalyze the breakdown of H2O2 and produce oxygen, thereby significantly alleviating the hypoxic state of tumor tissues. The oxygen generated not only enhances the activity of oxygen-sensitive drugs required for PDT but also promotes local oxidative stress, which ultimately leads to apoptosis and destruction of cancer cells. In summary, as a new cancer treatment strategy, peptide-modified gold nanoclusters combine the specificity of peptides with the excellent physicochemical properties of gold nanoclusters, showing broad application prospects.
Table 1. Peptide modification service at Creative Peptides
PEG modification improves pharmacokinetic properties
PEGylation of peptides and proteins not only helps to shield antigens and immunogenic epitopes, but also effectively prevents the recognition and degradation of proteolytic enzymes, thereby improving their stability and bioavailability. PEGylation can also significantly increase the apparent size of a peptide or protein, and this increased molecular weight helps to reduce the renal filtration rate and prolong its circulation time in the body. For example, Oncaspar® is an asparaginase that has successfully applied PEGylation technology. Through PEGylation, the half-life of Oncaspar® is significantly extended, resulting in a significant improvement in its efficacy and pharmacokinetic properties in the treatment of acute lymphoblastic leukemia. The successful application of this technology has not only led to a breakthrough in the field of cancer treatment, but also provided a powerful paradigm for other treatment options that require enhanced drug stability and biological activity.
Cyclization modification to Improve biochemical properties
Cyclization modification is an important biochemical strategy that forms a cyclic structure by linking amino acid residues inside a peptide molecule. This structural adjustment can not only enhance the structural stability of the peptide molecule, but also significantly improve its biological activity and pharmacological properties. For example, Gomezine is an 18-residue peptide isolated from the Brazil spider Acanthoscurria gomesiana and has a wide range of biological activities, including anticancer, antibacterial, and antifungal effects. Studies have shown that through cyclization, Gomez's stability in vitro is significantly improved, and its cytotoxicity to cancer cells is also enhanced, while its toxicity to non-cancer cells is significantly reduced. This improvement not only provides a more reliable basis for the application of Gomezine in treatment, but also provides an important reference and method for the development and optimization of other peptide drugs.
Polymer modification improves antimicrobial efficacy
Grafting β NM40CH60-peptide polymers with pro-endothelialization functions onto polyurethane (TPU) surfaces is an innovative biomaterial design strategy. This modification not only demonstrated broad-spectrum contact bactericidal activity against Gram-positive and Gram-negative bacteria, effectively reducing the risk of infection during artificial vascular implantation, but also maintained the excellent endothelial cell-selective adhesion function of the material. The combination of these dual functions allows the modified TPU to promote good biocompatibility and healing processes in surrounding tissues while responding to the challenge of external pathogens. This technological advancement not only provides new ideas for improving the performance of medical devices such as artificial blood vessels, but also lays the foundation for the development of safer and more effective biomedical materials in the future.
Peptide modification for polyvalent vaccines
Peptide modification plays an important role in vaccine design, especially in the development of multivalent vaccines. By combining multiple pathogen epitopes into a single peptide structure, the immune system can be simultaneously stimulated to respond to multiple pathogens, thereby providing broader protection. For example, a peptide vaccine containing epitopes of influenza virus and Streptococcus pneumoniae can not only trigger an immune response against both pathogens, but also improve immune protection. This strategy not only simplifies the vaccination process, but is also expected to make significant progress in the prevention of infectious diseases, especially for populations that need to deal with the threat of multiple pathogens, and has important clinical and epidemiological implications.
Summary
Peptide modifications have a wide range of application potential in the field of drug development. By adjusting the structure and chemistry of peptides, the biological activity, stability, and targeting of drugs can be significantly enhanced, thereby improving therapeutic efficacy and reducing side effects. In general, peptide modification technology not only expands the technical means of drug development, but also brings more possibilities and hopes for new drug research and development.
References
- Su, Dongdong, et al., Peptide and protein modified metal clusters for cancer diagnostics. Chemical Science 11.22 (2020): 5614-5629.
- Yin, Hong, et al., iRGD as a tumor‑penetrating peptide for cancer therapy. Molecular medicine reports 15.5 (2017): 2925-2930.
- Roberts, M. J., et al., Chemistry for peptide and protein PEGylation. Advanced drug delivery reviews 54.4 (2002): 459-476.
- Zhang, Sanke, et al., Thermoresponsive Peptide Fused L-Asparaginase with Mitigated Immunogenicity and Enhanced Efficacy in Treating Hematologic Malignancies. Advanced Science 10.23 (2023): 2300469.
- Chan, Lai Yue, et al., Cyclization of the antimicrobial peptide gomesin with native chemical ligation: influences on stability and bioactivity. ChemBioChem 14.5 (2013): 617-624.
- Skwarczynski, Mariusz, and Istvan Toth. Peptide-based synthetic vaccines. Chemical science 7.2 (2016): 842-854.
