Designing metallodrugs with nuclease and protease activity
| Autor: | Octavio L. Franco, Caleb M Agbale, Isaac K. A. Galyuon, Marlon H. Cardoso |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Amino terminal
medicine.medical_treatment Biophysics Human immunodeficiency virus (HIV) Antineoplastic Agents 010402 general chemistry medicine.disease_cause 01 natural sciences Biochemistry Catalysis Biomaterials Anti-Infective Agents Organometallic Compounds medicine Humans Nuclease Protease biology Low toxicity 010405 organic chemistry Esterases Metals and Alloys Drug Resistance Microbial 0104 chemical sciences Chemistry (miscellaneous) Drug Design biology.protein Peptide Hydrolases |
| Zdroj: | Metallomics. 8:1159-1169 |
| ISSN: | 1756-591X 1756-5901 |
| DOI: | 10.1039/c6mt00133e |
| Popis: | The accidental discovery of cisplatin some 50 years ago generated renewed interest in metallopharmaceuticals. Beyond cisplatin, many useful metallodrugs have been synthesized for the diagnosis and treatment of various diseases, but toxicity concerns, and the propensity to induce chemoresistance and secondary cancers make it imperative to search for novel metallodrugs that address these limitations. The Amino Terminal Cu(ii) and Ni(ii) (ATCUN) binding motif has emerged as a suitable template to design catalytic metallodrugs with nuclease and protease activities. Unlike their classical counterparts, ATCUN-based metallodrugs exhibit low toxicity, employ novel mechanisms to irreversibly inactivate disease-associated genes or proteins providing in principle, a channel to circumvent the rapid emergence of chemoresistance. The ATCUN motif thus presents novel strategies for the treatment of many diseases including cancers, HIV and infections caused by drug-resistant bacteria at the genetic level. This review discusses their design, mechanisms of action and potential for further development to expand their scope of application. |
| Databáze: | OpenAIRE |
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