Cyclic peptides have emerged as a prominent class of therapeutic agents, representing about two-thirds of the 60 or so FDA- and EMA-approved drugs targeting a diverse array of diseases. Cyclic peptides have several advantages over linear peptides, particularly their enhanced pharmacokinetic and pharmacodynamic properties. Advancements in chemical synthesis, especially the application of computational modeling, alongside the development of robust in vitro assays, have significantly accelerated the discovery and development of cyclic peptides.
CyclicPepedia is a database that encompasses both synthetically derived and naturally occurring cyclic peptides, totaling 8,744 known cyclic peptides. Most of these are toxins, cyclotides, and orbitides.
It offers a wealth of information on cyclic peptides, including summaries, structures, sequences, properties, assays, targets, prediction tools, manufacturers, external links, and relevant literature. It also provides structure-sequence (Struc2Seq) conversion, structure-sequence format transformation, and peptide property predictions.
Peptides are collected from various sources:
PubChem: 2,535
DrugBank: 91
UniProt: 605
CyBase: 1,236
DPL: 88
APD: 204
ConoServer: 3,416
DRAMP: 914
Norine: 576
The database includes 5,465 (62.50%) natural and 1,537 (17.58%) synthetic cyclic peptides. These cyclic peptides have sequence lengths of 40 amino acids or fewer, with a higher number of natural peptides having lengths greater than 20 amino acids compared to synthetic ones.
CyclicPepedia is a good resource for researchers, providing benchmark datasets for two key areas:
1️⃣ De novo design and engineering of new functional cyclic peptides
2️⃣ Development of deep learning-based tools for cyclic peptide applications.
Importance of Peptides in Drug Discovery
Peptides play a crucial role in drug discovery due to their ability to mimic natural biological processes. They offer high specificity and potency, making them suitable for targeting a wide range of diseases, including cancers, metabolic disorders, and infectious diseases. Their inherent biocompatibility and low toxicity further enhance their appeal as therapeutic agents.
Examples of Peptide-Based Drugs
Several peptide-based drugs have been successfully developed and approved. For instance, Cyclosporine, a cyclic peptide, is used as an immunosuppressant in organ transplantation. Other notable examples include the cyclic peptide antibiotic Vancomycin and the anti-HIV drug Enfuvirtide. These drugs exemplify the therapeutic potential and versatility of peptide-based treatments.
Challenges with Peptides and Cyclic Peptides for Therapeutic Developments
Despite their advantages, developing peptide-based therapeutics poses challenges. Peptides are often susceptible to enzymatic degradation, leading to short half-lives. Additionally, their large molecular size can result in poor cell permeability and limited oral bioavailability. Overcoming these obstacles requires innovative drug delivery systems and modifications to enhance peptide stability and bioavailability.
Peptides and Cyclic Peptides as Drugs and Biologics
The future of peptide-based therapeutics is promising, with advancements in peptide engineering and delivery technologies paving the way for new treatments. Cyclic peptides, in particular, hold great potential due to their stability and ability to target challenging proteins. Continued research and development in this field are expected to lead to the discovery of novel peptide-based drugs and biologics, addressing unmet medical needs and improving patient outcomes.
Next Update Plan Release: 2024.06.30 (V1.4.0): Update plan
Integration of Artificial Intelligence Tools into CyclicPepedia
🎯 Utilize AI models to predict high-affinity binding targets
🎯 Predict pharmacological properties, toxicity, and biological activities of cyclic peptides
🎯 Use AlphaFold2 and AfCycDesign to predict 3D structures of cyclic peptides and protein-peptide complex structures
Resources
- Paper: CyclicPepedia: a knowledge base of natural and synthetic cyclic peptides
- CyclicPepedia webserver
- Download full CyclicPepedia
- CyclicPepedia (V1.3.1) Tutorial
- Fosgerau, K., & Hoffmann, T. (2015). Peptide therapeutics: current status and future directions. Drug Discovery Today, 20(1), 122-128.
- Fairlie, D. P., et al. (1995). Cyclic peptides as mimics of protein structure and function. Current Opinion in Structural Biology, 5(4), 432-439.
- Ganesan, A. (2008). Natural product drug discovery: past and future. Chemical Communications, (46), 4817-4830.
