Welcome to the documentation for CPPsite, a comprehensive and manually curated database of experimentally validated cell-penetrating peptides (CPPs). This resource is designed to centralize information scattered across literature and patents to help researchers understand the properties of these peptides and develop effective delivery vehicles for therapeutic molecules.
Database URL: https://webs.iiitd.edu.in/raghava/cppsite1/
Gautam, A., Singh, H., Tyagi, A., Chaudhary, K., Kumar, R., Kapoor, P., & Raghava, G. P. S. (2012). CPPsite: a curated database of cell penetrating peptides. Database, Vol. 2012, Article ID bas015. https://doi.org/10.1093/database/bas015
This dataset can also be found on Zenodo at https://doi.org/10.5281/zenodo.20063826
CPPsite provides systematic information on 843 experimentally validated CPP entries, derived from 741 unique sequences. These peptides have the unique ability to cross the eukaryotic plasma membrane, which is otherwise selectively permeable and often impermeable to large therapeutic molecules like DNA and proteins.
The database integrates data from:
- Research Articles: Over 500 articles were searched, with 83 selected for high-quality experimental data.
- Patents: 50 patents were searched, with 20 utilized for the database.
Each entry in CPPsite provides extensive details, including:
- Peptide Basics: ID, Name, Sequence, and Origin (Protein derived, Chimeric, or Synthetic).
- Experimental Details: Uptake efficiency, uptake mechanism (Endocytic vs. Non-endocytic), and sub-cellular localization.
- Chemical Modifications: Chirality (L-form, D-form, Mixed), N- and C-terminal modifications, and cyclic status.
- Cell Lines: Information on approximately 85 different cell lines used for validation, with HeLa, CHO, and NIH-3T3 being the most common.
- Structure Prediction: 3D structures predicted using PEPstr and secondary structures assigned via DSSP.
- Physicochemical Properties: Calculated values for molecular weight, isoelectric point (pI), hydrophobicity, hydrophilicity, and net charge.
- Compositional Analysis: Tools to browse amino acid frequency and composition, revealing that Arginine (Arg) and Lysine (Lys) are highly preferred in CPPs.
- Similarity Searching: BLAST search, Smith-Waterman algorithm for small peptides, and an "Identical Residues" tool.
- Peptide Mapping: Tool to map known CPPs onto a user-provided polypeptide or protein sequence.
- Visualization: Integration with Jmol for interactive 3D structure viewing.
The 843 entries are categorized by several major fields:
- Origin: Protein derived (522), Synthetic (278), and Chimeric (43).
- Nature: Cationic (180), Amphipathic (194), and others including antimicrobial and cysteine-rich.
- Chirality: Predominantly L-form (777), followed by D-form (34), Modified (21), Mixed (11), and Cyclic (8).
- Uptake Mechanism: Documented for 358 peptides (174 Endocytic; 184 Non-endocytic), while 470 remain unknown.
- Drug Delivery Design: Selecting the most efficient CPP based on desired physicochemical properties and cell-line specificity.
- Model Development: Using the curated dataset to train machine learning models for predicting effective cell-penetrating peptides.
- Structural Studies: Exploiting 3D structural data for docking studies or molecular dynamics of peptide-membrane complexes.
Prof. G. P. S. Raghava (Corresponding Author) raghava@iiitd.ac.in
IIIT Delhi
CPPsite is a freely available open-source database. It is distributed under the Creative Commons Attribution License (CC BY 3.0). Researchers are encouraged to submit new experimentally validated CPP entries via the online HTML form to assist in regular updates.