Development of HER2-antagonistic peptides as novel anti-breast cancer drugs by in silico methods
| Autor: | Naruhiko Mizuta, Satoshi Takahashi, Atsushi Yoshimori, Ryoko Takasawa, Hiroo Nakajima, Koichi Sakaguchi, Ikuya Fujiwara, Sei-ichi Tanuma |
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| Rok vydání: | 2007 |
| Předmět: |
chemistry.chemical_classification
medicine.drug_class Cell growth In silico Peptide General Medicine Biology Pharmacology Monoclonal antibody Oncology chemistry Apoptosis medicine biology.protein Cancer research PTEN Phosphorylation Pharmacology (medical) Radiology Nuclear Medicine and imaging skin and connective tissue diseases Protein kinase B |
| Zdroj: | Breast Cancer. 15:65-72 |
| ISSN: | 1880-4233 1340-6868 |
| DOI: | 10.1007/s12282-007-0018-8 |
| Popis: | An antagonistic peptide called HRAP that binds to the human HER2 molecule was designed by our computational method. In silico docking study demonstrated the specific interaction of HRAP with the dimerization domain in the HER2 molecule. Interestingly, HRAP inhibited proliferation of HER2-overexpressed human breast cancer cell lines. However, it had little cellular cytotoxicity (apoptosis inducibility). The cell proliferation inhibition was associated with the suppression of phosphorylation of PTEN and Akt. Thus, HRAP is the first HER2-binding small peptide antagonist rationally designed by a computer-aided SBDD method and is useful for the development of peptide mimetics to generate novel anti-breast cancer drugs. |
| Databáze: | OpenAIRE |
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