Defining interacting partners for drug discovery.
Over the past few years, several technologies have been developed to determine interacting partners of proteins. The techniques fall into two broad categories: direct and indirect. Experimental techniques have been developed to directly probe protein interactions by monitoring protein-binding events. These techniques include the two-hybrid approach, protein fragment complementation assays, co-purification techniques and protein chips. In addition to these methodologies, several approaches have also emerged over the past few years to deduce indirect couplings between proteins. These couplings do not necessarily imply that two proteins are bound within the cell; however, they do provide evidence that perturbing one protein is likely to significantly perturb the function of its partner. These couplings may be deduced by studying the evolution of protein pairs, estimating the degree of correlated transcription of two genes, searching for synthetic lethal pairs, or identifying the chromosomal binding sites of transcriptional regulators. In all cases, protein interactions and protein couplings are being used to advance drug discovery by providing detailed information on protein functions, and by suggesting novel targets that act within biochemical pathways implicated in disease.
Pellegrini
Matteo
M
Protein Pathways, Inc., 21111 Oxnard Blvd, Woodland Hills, CA 91367, USA. matteope@proteinpathways.com
D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004591:Electrophoresis, Polyacrylamide Gel; D005804:Genes, Lethal; D005813:Genes, Synthetic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011506:Proteins / Q000302:isolation & purification; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D011506:Proteins; D011993:Recombinant Fusion Proteins