CPPsite 2.0 is an updated and significantly expanded version of the manually curated database of cell-penetrating peptides (CPPs). This resource is designed to support the scientific community in developing effective intracellular delivery vehicles for various therapeutic molecules, including drugs, proteins, and nucleic acids.
Web Server: https://webs.iiitd.edu.in/raghava/cppsite/ Cite Piyush Agrawal, Sherry Bhalla, Salman Sadullah Usmani, Sandeep Singh, Kumardeep Chaudhary, Gajendra P. S. Raghava, Ankur Gautam, CPPsite 2.0: a repository of experimentally validated cell-penetrating peptides, Nucleic Acids Research, Volume 44, Issue D1, 4 January 2016, Pages D1098–D1103, https://doi.org/10.1093/nar/gkv1266
This dataset is also available on Zenodo at https://doi.org/10.5281/zenodo.20086676
Cell-penetrating peptides are short peptides (usually 10–30 amino acids) with the ability to gain access to the interior of almost any cell type. CPPsite 2.0 consolidates information from research papers and patents, providing a centralized platform to explore the sequences, modifications, and experimental validations of these peptides.
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Data Expansion: The current version holds approximately 1,850 peptide entries, nearly doubling the content of the previous version.
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Recent Curation: The updated data were curated from literature published between 2012 and 2015.
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Focus on Diversity: A major focus of this update is the inclusion of CPPs with diverse chemical modifications.
- Please convert all the ".fasta" files in Natural and non natural folders to ".rtf" format or download it directly from the server.
The database now provides detailed information on various modifications used to enhance the stability and uptake of peptides:
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Non-Natural Residues: Inclusion of D-amino acids and other non-natural amino acid analogs.
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Terminal Modifications: Extensive data on N-terminal (e.g., acetylation, fatty acid attachment) and C-terminal (e.g., amidation) modifications.
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Complex Architectures: Information on cyclic, branched, and stapled peptides.
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Conjugations: Data on peptides linked to various cargoes, including lipids, linkers, and fluorophores.
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3D Structures: Provides experimental structures from the PDB or predicted models generated using PEPstrMOD, which can handle natural and non-natural residues.
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Uptake Mechanism: Catalogs experimentally determined mechanisms such as endocytosis or direct translocation.
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Subcellular Localization: Information on where the peptide localizes within the cell (e.g., nucleus, cytoplasm, mitochondria).
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Validation Context: Details on the cell lines and experimental conditions used to validate each CPP.
CPPsite 2.0 offers a suite of web-based tools for data analysis:
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Search and Browse: Query by peptide name, PMID, sequence, or specific chemical modifications.
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Similarity Search: Integrated BLAST and Smith-Waterman tools for sequence-based matching.
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Structure Visualization: Interactive 3D visualization of peptide structures.
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Delivery Vehicle Design: Identifying modified peptides with high uptake efficiency and low toxicity for drug delivery.
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Machine Learning: Utilizing the curated dataset to train advanced prediction models for CPP activity.
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Mechanistic Research: Analyzing how specific chemical modifications influence the cellular entry pathways of peptides.
Prof. Gajendra P. S. Raghava (Corresponding Author)
Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh, India.
CPPsite 2.0 was supported by the Council of Scientific and Industrial Research (CSIR) and the Department of Biotechnology (DBT), Government of India. The project is part of the Open Source Drug Discovery (OSDD) initiative.