Advances in protein chemistry and structural biology · 2019
Protein-protein complexes as targets for drug discovery against infectious diseases.
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Akhter Yusuf, Hussain Razak
Аннотация
Antibiotics are therapeutic agents against bacterial infections, however, the emergence of multiple and extremely drug-resistant microbes (Multi-Drug Resistant and Extremely Drug-Resistant) are compromising the effectiveness of the currently available treatment options. The drug resistance is not a novel crisis, the current pace of drug discovery has failed to compete with the growth of MDR and XDR pathogenic strains and therefore, it is highly central to find out novel antimicrobial drugs with unique mechanisms of action which may reduce the burden of MDR and XDR pathogenic strains. Protein-protein interactions (PPIs) are involved in a countless of the physiological and cellular phenomena and have become an attractive target to treat the diseases. Therefore, targeting PPIs in infectious agents may offer a completely novel strategy of intervention to develop anti-infective drugs that may combat the ever-increasing rate of drug resistant strains. This chapter describes how small molecule candidate inhibitors that are capable of disrupting the PPIs in pathogenic microbes and it could be an alternative lead discovery strategy to obtain novel antibiotics. Over the last three decades, there has been increasing efforts focused on the manipulation of PPIs in order to develop novel therapeutic interventions. The diversity and complexity of such a complex and highly dynamic systems pose many challenges in targeting PPIs by drug-like molecules with necessary selectivity and potency. Traditional and novel drug discovery strategies have provided tools for designing and assessing PPI inhibitors against infectious diseases.
Предметные рубрики MeSH
Allosteric SiteAnti-Bacterial AgentsBacterial InfectionsBacterial ProteinsCarrier ProteinsCell Cycle ProteinsCytoskeletal ProteinsDNA-Directed DNA PolymeraseDrug Delivery SystemsDrug DiscoveryDrug Resistance, Multiple, BacterialEscherichia coli ProteinsHumansModels, MolecularProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction MappingRibosomal ProteinsTranscription Factors