Cell-penetrating peptides (CPPs) are a class of small molecule peptides consisting of no more than 30 amino acids. They have been widely used for intracellular delivery of various agents ranging from small molecules to proteins, peptides, range of pharmaceutical nanocarriers and imaging agents[1]. In vivo and in vitro studies have shown that CPPs can mediate the membrane-penetrating effects of a variety of carriers, are non-irritating, and have no toxic effects on host cells within a certain concentration range. Furthermore, CPPs become potential tools to study the primary mechanisms of cellular entry across the plasma membrane. Therefore, CPPs are considered promising devices for medical and biotechnological development. Alfa Chemistry provides comprehensive CPP synthesis services to cater to the growing demand for these unique molecules. We have a team of experienced chemists and state-of-the-art facilities to enable the efficient and high-quality synthesis of CPPs.
Fig.1 CPPs cross cell membranes to deliver various agents into cells[1].
What We Offer
We offer a range of CPP synthesis services to ensure that our clients receive CPPs that meet their specific requirements for research or therapeutic applications. Whether you need a novel CPP synthesized from scratch or require assistance in optimizing an existing peptide for enhanced cellular uptake, our experienced team is here to help. Our services include:
- Design and optimization. Our team of experts can work with clients to design and optimize CPPs to ensure maximum efficacy and efficiency in delivering therapeutic molecules to target cells.
- Custom synthesis. We offer custom synthesis of CPPs using state-of-the-art peptide synthesis techniques, including solid-phase synthesis and liquid-phase synthesis.
- Modification and conjugation. We can modify and conjugate CPPs with a variety of molecules, including fluorophores, antibodies, and drug molecules, to enhance their targeting and delivery capabilities.
- Purification and characterization. Our services also include purification and characterization of CPPs to ensure high purity and quality of the final product.
- Cell-based assays. We can perform cell-based assays to evaluate the efficacy and bioactivity of CPPs in delivering therapeutic molecules to target cells.
Common CPPs
Items | Source | Sequence |
Tat family | - | - |
Tat (48-60) | HIV-1 protein | GRKKRRQRRRPPQQ |
Oligoarginine | - | - |
Penetralia family | - | - |
p-Antp | Antermapedia homeodomain | RQIKIWFQNRRMKWKK |
Plsl | Igl-1 homeodomain | RVIRVWFQNKRCKDKK |
Chimeric CPPs | - | - |
Transportan | Galanin-mastoparan | GWTLNSAGYLLGKINLKALAALAKKIL |
MPG peptides | - | - |
Transmembrane Mechanism of CPPs
The exact mechanism by which CPPs enter cells, known as the transmembrane mechanism, is not fully elucidated and seems to vary depending on the specific CPP sequence, the cargo they carry, and the type of cells they are targeting. However, several common mechanisms have been proposed[2]:
- Direct translocation. This mechanism suggests that CPPs interact directly with the lipid bilayer and induce transient pores or disruptions in the membrane, allowing them to pass through. However, this mechanism is debated as some studies suggest that CPPs do not significantly disrupt the cell membrane.
- Endocytosis. This mechanism involves the uptake of CPPs through endocytic pathways, such as clathrin-mediated endocytosis, caveolae-mediated endocytosis, or macropinocytosis. Once inside the endosome, the cargo may escape into the cytoplasm through endosomal escape mechanisms like pH-dependent disruption, membrane destabilization, or interactions with specific cellular components.
- Receptor-mediated uptake. Some CPPs may interact with cell surface receptors or co-receptors, triggering specific uptake pathways that lead to internalization. This mechanism can enhance the selectivity and efficiency of CPP-mediated cargo delivery.
Service Process

References
- Sawant, R.; Torchilin, V. Intracellular transduction using cell-penetrating peptides. Mol. BioSyst. 2010, 6, 628-640.
- Bechara, C.; Sagan, S. Cell-penetrating peptides: 20 years later, where do we stand? FEBS Letters. 2013, 587, 1693-1702.