Targeting Protein Folding: A Novel Approach for the Treatment of Pathogenic Bacteria
| Autor: | Mitali Sarkar-Tyson, Nicolas J Scheuplein, Nicole M. Bzdyl, Ulrike Holzgrabe, Theresa Lohr, Emily A Kibble |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Protein Folding
Virulence Computational biology Gram-Positive Bacteria medicine.disease_cause 01 natural sciences Protein Structure Secondary Bacterial protein 03 medical and health sciences Drug Delivery Systems Antibiotic resistance Bacterial Proteins Immunophilins Gram-Negative Bacteria Drug Discovery medicine Animals Humans 030304 developmental biology 0303 health sciences biology Chemistry SUPERFAMILY Pathogenic bacteria Bacterial Infections biology.organism_classification Anti-Bacterial Agents Protein Structure Tertiary 0104 chemical sciences 010404 medicinal & biomolecular chemistry Molecular Medicine Protein folding Bacteria |
| Zdroj: | Journal of Medicinal Chemistry. 63:13355-13388 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/acs.jmedchem.0c00911 |
| Popis: | Infectious diseases are a major cause of morbidity and mortality worldwide, exacerbated by increasing antibiotic resistance in many bacterial species. The development of drugs with new modes of action is essential. A leading strategy is antivirulence, with the aim to target bacterial proteins that are important in disease causation and progression but do not affect growth, resulting in reduced selective pressure for resistance. Immunophilins, a superfamily of peptidyl-prolyl cis-trans isomerase (PPIase) enzymes have been shown to be important for virulence in a broad-spectrum of pathogenic bacteria. This Perspective will provide an overview of the recent advances made in understanding the role of each immunophilin family, cyclophilins, FK506 binding proteins (FKBPs), and parvulins in bacteria. Inhibitor design and medicinal chemistry strategies for development of novel drugs against bacterial FKBPs will be discussed. Furthermore, drugs against human cyclophilins and parvulins will be reviewed in their current indication as antiviral and anticancer therapies. |
| Databáze: | OpenAIRE |
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