Anti-Angiogenic Peptides for Cancer Therapeutics
Elena V. Rosca, Jacob E. Koskimaki, Corban G. Rivera, Niranjan B. Pandey, Amir P. Tamiz and Aleksander S. Popel
Affiliation: Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, 720 Rutland Avenue, 611 Traylor Bldg, Baltimore, MD 21205, USA.
Keywords: Angiogenesis, animal model, computational biology, inhibitor, in vitro model, peptidomimetics, tumor vasculature, tumor, angiogenesis-dependent diseases, microvessel formation, cancer, anti-angiogenic peptides, non-natural amino acid substitutions, anti-cancer agents
Peptides have emerged as important therapeutics that are being rigorously tested in angiogenesis-dependent diseases due to their low toxicity and high specificity. Since the discovery of endogenous proteins and protein fragments that inhibit microvessel formation (thrombospondin, endostatin) several peptides have shown promise in pre-clinical and clinical studies for cancer. Peptides have been derived from thrombospondin, collagens, chemokines, coagulation cascade proteins, growth factors, and other classes of proteins and target different receptors. Here we survey recent developments for anti-angiogenic peptides with length not exceeding 50 amino acid residues that have shown activity in pre-clinical models of cancer or have been tested in clinical trials; some of the peptides have been modified and optimized, e.g., through L-to-D and non-natural amino acid substitutions. We highlight technological advances in peptide discovery and optimization including computational and bioinformatics tools and novel experimental techniques.
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