title: Designing metallodrugs with nuclease and protease activity.
abstract: 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.
authors.affiliation: School of Biological Sciences, College of Agriculture and Natural Sciences, University of Cape Coast, Cape Coast, Ghana and S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, 79117-900 Campo Grande, MS, Brazil. ocfranco@gmail.com.
authors.forename: Caleb Mawuli
authors.initials: CM
authors.lastname: Agbale
authors.affiliation: S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, 79117-900 Campo Grande, MS, Brazil. ocfranco@gmail.com and Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, 70719-100 Brasília, DF, Brazil and Programa de Pós-Graduação em Patologia Molecular, Faculdade de Medicina, Universidade de Brasília, 70910-900 Brasília, DF, Brazil.
authors.forename: Marlon Henrique
authors.initials: MH
authors.lastname: Cardoso
authors.affiliation: School of Biological Sciences, College of Agriculture and Natural Sciences, University of Cape Coast, Cape Coast, Ghana.
authors.forename: Isaac Kojo
authors.initials: IK
authors.lastname: Galyuon
authors.affiliation: S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, 79117-900 Campo Grande, MS, Brazil. ocfranco@gmail.com and Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, 70719-100 Brasília, DF, Brazil and Programa de Pós-Graduação em Patologia Molecular, Faculdade de Medicina, Universidade de Brasília, 70910-900 Brasília, DF, Brazil.
authors.forename: Octávio Luiz
authors.initials: OL
authors.lastname: Franco
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D015195:Drug Design; D004352:Drug Resistance, Microbial; D004950:Esterases / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D004950:Esterases; D010447:Peptide Hydrolases