title: Drug Target Validation Methods in Malaria - Protein Interference Assay (PIA) as a Tool for Highly Specific Drug Target Validation.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Sciences, University of Saõ Paulo, Avenida Professor Lineu Prestes 1374, Saõ Paulo - SP 05508-000, Brazil.
authors: Kamila A
authors: KA
authors: Meissner
authors: Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9700 AD, Groningen. Netherlands.
authors: Sergey
authors: S
authors: Lunev
authors: Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9700 AD, Groningen. Netherlands.
authors: Yuan-Ze
authors: YZ
authors: Wang
authors: Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Sciences, University of Saõ Paulo, Avenida Professor Lineu Prestes 1374, Saõ Paulo - SP 05508-000, Brazil.
authors: Marleen
authors: M
authors: Linzke
authors: Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9700 AD, Groningen. Netherlands.
authors: Fernando
authors: F
authors: de Assis Batista
authors: Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Sciences, University of Saõ Paulo, Avenida Professor Lineu Prestes 1374, Saõ Paulo - SP 05508-000, Brazil.
authors: Carsten
authors: C
authors: Wrenger
authors: Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9700 AD, Groningen. Netherlands.
authors: Matthew R
authors: MR
authors: Groves
mesh_terms: D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D003434:Crossing Over, Genetic; D016503:Drug Delivery Systems; D055808:Drug Discovery; D055785:Gene Knockdown Techniques; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics; D011506:Proteins / Q000378:metabolism*
chemical_list: D000962:Antimalarials; D011506:Proteins
keywords: Drug target validation; in vivo specificity; malaria; oligomerisation; protein Interference; protein: protein interactions