Introduction to pH-Sensitive Biomolecule Discovery by Phage Display

Different parts of the body have different pH values, and diseases can cause changes in the pH of specific areas. The affinity and specificity of protein-protein or protein-antibody interactions can be regulated by the external environment's pH. pH binding affinity sensitivity plays a crucial role in biological processes. By utilizing the properties of the pH at the targeting site, we can enhance the action and specificity of antibody drugs. In addition, pH-sensitive bioactive peptides also play a vital role in biological research, including pH-sensitive cleavage peptides and pH-sensitive peptide drug delivery systems. Based on our rich field experience and phage display platform, Creative Biolabs provides comprehensive services to support the development of pH-sensitive biomolecules.

Antibodies. (Creative Biolabs Authorized)

pH-Sensitive Biomolecules

Lytic peptides are a group of cationic peptides characterized by high levels of arginine and lysine, with these basic amino acids playing a key role in peptide membrane partitioning and significantly contributing to peptide bioactivity. They primarily act on cell membranes without entering the cell, causing cell lysis. pH-controlled aggregation and solubilization are responsible for the pH-dependent membrane lytic activity of these peptides. Studies on the interaction of lytic peptides with cells have demonstrated that the shift of peptides to the binding plane and their insertion into the membrane are crucial for inducing cell membrane lysis in cleavage peptides. In contrast, pH-sensitive lytic peptides can exhibit up to a 30-fold increase in activity in response to reduced medium pH.

Furthermore, pH sensitivity provides a new direction for tumor targeting. Cancer cells typically have higher metabolism and cell surface buffering capacity, potentially resulting in more acidic surface pHs compared to normal cells. Low pH has wide spread effects on the tumor microenvironment, leading to immunosuppression, inflammation, immune escape, and disease progression. At acidic pH, effector immune cells such as T cells and NK cells undergo a reversible state of incompetence followed by apoptosis, while myeloid-derived suppressor cells sustain tumor growth and reduce drug responses. They might also hinder immunotherapy for "cold tumors." However, scientists have developed new tumor-targeting drugs based on acidic pH, such as pH-sensitive monoclonal antibodies and cell therapies, offering new hope for tumor treatment. Institutions are developing selective antibody and CAR-T cell therapy technologies based on acidic pH, potentially enhancing the tumor microenvironmental targeting of antibodies and CAR-T cells while reducing off-tumor toxicity.

pH sensitivity is also well used in the field of peptide drug delivery systems. Cell penetrating peptides are short cationic peptides consisting of 10-30 amino acid residues. Cell penetrating peptides can mediate the entry of a variety of substances into cells, such as DNA, proteins, antibodies, visualizers, nanoparticles, and liposomes. However, the in vivo application of cell-penetrating peptides is limited by their poor selectivity, in vivo systemic toxicity due to high positive charge, and stability issues. To solve this problem, scientists have tried many strategies. It has been reported that pH sensitivity can address the limitations of cell-penetrating peptides in tumor drug-targeted delivery. Scientists found that an acid-activated cell-penetrating peptide can selectively carry small molecule drugs, nanoparticles, micelles, polymers, oligonucleotides, proteins, or fluorescent marker molecules into tumor cells for various applications.

More Details on pH-Sensitive Biomolecules Discovery by Phage Display

Introduction to pH-Sensitive Bioactive Peptide Discovery by Phage Display
Introduction to pH-Sensitive Monoclonal Antibody Discovery by Phage Display

Creative Biolabs has a wealth of knowledge and experience in pH-sensitive biomolecules. We would be happy to share with you our knowledge and experience in pH-sensitive biomolecule discovery with phage display.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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