Cyclic peptides are of significant importance in drug development due to their unique structural and functional properties. Their cyclic structure enhances stability and target specificity, enabling resistance to protease degradation and offering a longer half-life in vivo. Additionally, cyclic peptides exhibit considerable structural diversity, allowing the creation of vast molecular libraries through various amino acid combinations and modifications, improving target recognition. Compared to traditional small molecule drugs or antibodies, cyclic peptides offer advantages in synthesis and can target intracellular proteins, expanding their potential applications in biotechnology and medicine.
Creative Peptides offers a diverse range of high-quality cyclic peptide products to meet the needs of research and drug development. With advanced synthesis technologies and extensive expertise, we provide custom cyclic peptides of varying lengths and structures, including small, medium-sized, and modified peptides. Our cyclic peptide products are known for their superior stability, target specificity, and structural diversity, making them ideal for protein-protein interaction studies, drug screening, and applications in biotechnology and pharmaceuticals. Whether standard or customized, we deliver precise solutions tailored to your needs. Below are our cyclic peptide products:
Cyclic peptides are a diverse and important class of molecules, widely used in drug discovery, biotechnology, and materials science. Due to their unique cyclic structure and various bridging mechanisms, cyclic peptides offer high functionality and versatility. Depending on different criteria, cyclic peptides can be classified according to the type of bonds within the ring, the mode of cyclization, the chemical nature of the internal bridges, and the number of loops in the backbone. Below are the main classification schemes for cyclic peptides:
Homodetic Cyclic Peptides: These peptides are formed entirely by standard α-amide bonds (peptide bonds), with the entire cyclic structure composed solely of peptide linkages.
Heterodetic Cyclic Peptides: These peptides contain at least one non-α-amide bond in the ring, such as ester bonds, disulfide bonds, ether bonds, etc.
Head-to-Tail Cyclic Peptides: In these peptides, the N-terminal carboxyl group and C-terminal amine group form the ring.
Side-chain-to-Side-chain Cyclic Peptides: These peptides form a ring between two side chains of amino acids.
Side-chain-to-End Cyclic Peptides: These peptides involve cyclization where a side chain forms a bond with either the N-terminal or C-terminal.
Classical Bridges: These include lactam bridges, lactone bridges, and disulfide bridges, which are commonly found in cyclic peptide drugs and antimicrobial peptides.
Non-Classical Bridges: These include ether bridges, alkene bridges, thioether bridges, etc., typically found in recently synthesized multifunctional cyclic peptides.
Single-Loop Cyclic Peptides: These peptides consist of a single closed loop.
Double-Loop Cyclic Peptides: These peptides contain two interlinked or connected closed loops.
Multi-Loop Cyclic Peptides: These peptides contain three or more closed loops, forming more complex topologies.
Cyclic peptide molecules possess certain metabolic stability, cell-penetrating properties, and high specificity for target binding. They find applications in various disease treatment areas, including anti-infection (antibacterial, antifungal, antiviral), anticancer, platelet aggregation inhibition, antihypertensive, tyrosine kinase inhibition, cyclooxygenase inhibition, lipoxygenase inhibition, estrogen-like activity, immunosuppression, etc. These molecules can target extracellular membrane proteins such as GPCRs and ion channels, as well as intracellular membrane proteins such as PPIs.
Table 1. Cyclic Peptide Applications in Drug Therapy.
| Application Subcategory | Description |
|---|---|
| Antibacterial (Antibiotics) | There is a series of natural products and analogs used as antibiotics since 1948, such as bacitracin, polymyxin B, streptomycin, vancomycin, daptomycin, enopeptin, valinomycin, vancomycin, teicoplanin, dalbavancin, oritavancin, and telavancin. |
| Antifungal | Several cyclic peptide drugs for antifungal purposes have been introduced, including caspofungin, micafungin sodium, anidulafungin, and rezafungin. |
| Antiviral | Cyclic peptide drugs targeting HIV, such as palivizumab, golimumab, and fostamatinib, have been approved. |
| Targeting Intracellular Membrane Proteins | Two cyclic peptide drugs targeting intracellular membrane proteins have been approved: romidepsin and voclosporin. |
| Targeting Extracellular Proteins like GPCRs | Peptide inhibitors based on somatostatin modification, including octreotide, lanreotide, and pasireotide. Melanocortin agonists like bremelanotide and setmelanotide. Targeting chemokine receptor with motesanib. |
| Targeting Ion Channel Proteins | Ziconotide, a synthetic ω-conotoxin (ω-MVIIA), is a potent and selective blocker of N-type calcium channels. It was approved in 2004 for the treatment of severe chronic pain by reducing the release of neurotransmitters in the spinal dorsal horn. |
Cyclic cell-penetrating peptides (cCPPs) are a relatively new class of peptides with enormous potential in delivering therapeutic drugs intracellularly. They aim to treat challenging diseases, including multidrug-resistant bacterial infections, cancer, and HIV. Cell-penetrating peptides can be classified based on origin, physicochemical properties, or conformational differences. Based on origin, they can be protein-derived, chimeric, or synthetic. Based on conformation, they can be linear CPPs or cyclic CPPs. Based on physicochemical properties, they can be cationic CPPs, hydrophobic CPPs, amphipathic CPPs, etc.
Table 2. Application of cyclic peptides in drug delivery.
| Drug Delivery | Description |
|---|---|
| Commonly Used Efficient CPPs | For most CPPs, the efficiency of cell entry is low (<5%). Examples include CPP1, CPP9, and CPP12, with cell entry efficiencies of 20%, 62%, and 120%, respectively. High cell entry efficiency characteristics for CPPs include cyclic peptides, the presence of arginine and hydrophobic residues, and small ring sizes (≤9 aa). Some naturally occurring cyclic peptide scaffolds, such as SFTI-1, MCoTI-II, and Kalata B1, are commonly used for drug delivery. |
| Commonly Used Efficient CPPs | Cyclic CPPs can be grafted in five different ways for endocytic delivery: external loop, internal loop, double loop, reversible cyclization, and non-covalent complexation. |
| Deliverable "Cargo" | Deliverable "cargo" includes drug molecules, proteins, phosphorylated peptides, siRNA, fluorescent molecules, or other bioactive molecules. |
Protein-protein interactions (PPIs) play a crucial role in many biological and biochemical processes, including intracellular signaling and metabolism. Currently, there are 930,000 human PPIs identified, and targeting these interactions in drug development poses significant challenges. However, cyclic peptides demonstrate advantages in structure, stability, and cell-penetrating properties when targeting such interactions. Various methods are employed for studying PPI targets, such as using display technologies to screen high-throughput cyclic peptide compound libraries, studying the potential affinity molecules of target proteins, employing high-throughput virtual screening (HTVS) to identify candidate drug molecules from large compound libraries, and integrating deep learning (DL for protein structure prediction) and HTVS techniques, as seen in AlphaFold2.
Since 1994, five tumor diagnostic reagents based on somatostatin analogs have been developed, such as Indium In-111 Pentetreotide, Lutetium Lu 177 dotatate, Edotreotide gallium Ga-68, and Dotatate Copper Cu-64. Fluorescent cyclic peptides serve as excellent chemical scaffolds for constructing molecular imaging optical reagents. Besides possessing good physicochemical properties, they can be modified with various organic fluorescent groups, generating useful probes for specific protein (receptor or enzyme) bioassays. The RGD motif (arginine-glycine-aspartate sequence) has a long history in integrin transmembrane receptor targeting research.
Some cyclic peptides can assemble into tubular structures to form supramolecular cyclic peptide nanotubes, including α-peptides, β-peptides, α, γ-peptides, and cyclic peptides based on δ- and ε-amino acids. These cyclic peptide molecules self-assemble into nanotubes through intermolecular hydrogen bonding. They find applications in biological areas such as ion channels, lipid interactions, and membrane embedding. In addition to their applications in drug therapy, disease diagnosis, target research, drug delivery (such as molecular probes, PDC, etc.), cosmetics, supramolecular materials, etc., cyclic peptides also have various applications in industries such as catalysts, coatings; in biotechnology, such as separation and purification of biomolecules, biosensors; in the food and health supplement fields, such as functional ingredients.
Fig.1 Application direction of cyclic peptides (Creative Peptides Original).
Cyclic peptides are peptides with a closed-loop structure, formed through a covalent bond between the peptide's N- and C-termini or through side chain linkages. Unlike linear peptides, cyclic peptides have enhanced structural stability, resistance to enzymatic degradation, and often greater binding affinity to target molecules, making them ideal for therapeutic and diagnostic applications.
Cyclic peptides offer several advantages, such as improved stability, enhanced bioavailability, and higher specificity for target binding. These properties make them particularly valuable in drug discovery, as they can serve as effective modulators of protein-protein interactions and have shown potential in developing treatments for diseases like cancer, infections, and autoimmune disorder.
Creative Peptides employs several synthesis methods for cyclic peptides, including head-to-tail cyclization, side-chain cyclization, and disulfide bridge formation. Our team selects the most suitable approach based on the peptide sequence, desired cyclization type, and intended application to ensure high-quality and functional cyclic peptides.
Cyclic peptides are widely used in drug discovery, molecular biology, and diagnostic research. They are particularly valuable in the development of therapeutics for conditions like cancer, cardiovascular diseases, and infections. Due to their stability and binding affinity, cyclic peptides are also popular in biomarker detection and as tools for studying protein-protein interactions.
Yes, Creative Peptides offers expert consultation to help design custom cyclic peptides. Our team works closely with clients to determine the ideal peptide sequence, cyclization type, and any necessary modifications to ensure optimal performance for your specific research or therapeutic goals.
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