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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Drug Target Validation Methods in Malaria - Protein Interference Assay (PIA) as a Tool for Highly Specific Drug Target Validation

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Autor(es):
Meissner, Kamila A. ; Lunev, Sergey ; Wang, Yuan-Ze ; Linzke, Marleen ; Batista, Fernando de Assis ; Wrenger, Carsten ; Groves, Matthew R.
Número total de Autores: 7
Tipo de documento: Artigo de Revisão
Fonte: CURRENT DRUG TARGETS; v. 18, n. 9, p. 1069-1085, 2017.
Citações Web of Science: 4
Resumo

Background: The validation of drug targets in malaria and other human diseases remains a highly difficult and laborious process. In the vast majority of cases, highly specific small molecule tools to inhibit a proteins function in vivo are simply not available. Additionally, the use of genetic tools in the analysis of malarial pathways is challenging. These issues result in difficulties in specifically modulating a hypothetical drug target's function in vivo. Objective: The current ``toolbox{''} of various methods and techniques to identify a protein's function in vivo remains very limited and there is a pressing need for expansion. New approaches are urgently required to support target validation in the drug discovery process. Method: Oligomerisation is the natural assembly of multiple copies of a single protein into one object and this self-assembly is present in more than half of all protein structures. Thus, oligomerisation plays a central role in the generation of functional biomolecules. A key feature of oligomerisation is that the oligomeric interfaces between the individual parts of the final assembly are highly specific. However, these interfaces have not yet been systematically explored or exploited to dissect biochemical pathways in vivo. Results and Conclusion: This mini review will describe the current state of the antimalarial toolset as well as the potentially druggable malarial pathways. A specific focus is drawn to the initial efforts to exploit oligomerisation surfaces in drug target validation. As alternative to the conventional methods, Protein Interference Assay (PIA) can be used for specific distortion of the target protein function and pathway assessment in vivo. (AU)

Processo FAPESP: 12/12807-3 - Análise do estado redox e seu efeito sobre a proliferação de Plasmodium falciparum em eritrócitos geneticamente diferentes
Beneficiário:Kamila Anna Meissner
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 13/10288-1 - Análise da biogênese de organelas em Plasmodium falciparum por visualização celular em tempo real
Beneficiário:Carsten Wrenger
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 14/23330-9 - Análise morfológica da formação de apicoplasto em Plasmodium Falciparum
Beneficiário:Marleen Linzke
Linha de fomento: Bolsas no Brasil - Doutorado