title: Selectivity Determination of a Small Molecule Chemical Probe Using Protein Microarray and Affinity Capture Techniques.
abstract: Small molecule selectivity is an essential component of candidate drug selection and target validation. New technologies are required to better understand off-target effects, with particular emphasis needed on broad protein profiling. Here, we describe the use of a tritiated chemical probe and a 9000 human protein microarray to discern the binding selectivity of an inhibitor of the mRNA decapping scavenger enzyme DcpS. An immobilized m7GTP resin was also used to assess the selectivity of a DcpS inhibitor against mRNA cap-associated proteins in whole cell extracts. These studies confirm the exquisite selectivity of diaminoquinazoline DcpS inhibitors, and highlight the utility of relatively simple protein microarray and affinity enrichment technologies in drug discovery and chemical biology.
authors: Medicine Design, Pfizer , 610 Main Street, Cambridge, Massachusetts 02139, United States.
authors: Erik C
authors: EC
authors: Hett
authors: Medicine Design, Pfizer , East Point Road, Groton, Connecticut 06340, United States.
authors: Robert E
authors: RE
authors: Kyne
authors: Medicine Design, Pfizer , 610 Main Street, Cambridge, Massachusetts 02139, United States.
authors: Ariamala
authors: A
authors: Gopalsamy
authors: Rare Disease Research Unit, Pfizer , 610 Main Street, Cambridge, Massachusetts 02139, United States.
authors: Michael A
authors: MA
authors: Tones
authors: Medicine Design, Pfizer , 610 Main Street, Cambridge, Massachusetts 02139, United States.
authors: Hua
authors: H
authors: Xu
authors: Protein and Cell Analysis, Life Sciences Solutions, Thermo Fisher Scientific , 5781 Van Allen Way, Carlsbad, California 92008, United States.
authors: Guene L
authors: GL
authors: Thio
authors: Protein and Cell Analysis, Life Sciences Solutions, Thermo Fisher Scientific , 5781 Van Allen Way, Carlsbad, California 92008, United States.
authors: Edward
authors: E
authors: Nolan
authors: Medicine Design, Pfizer , 610 Main Street, Cambridge, Massachusetts 02139, United States.
authors: Lyn H
authors: LH
authors: Jones
mesh_terms: D002384:Catalysis; D002478:Cells, Cultured; D004722:Endoribonucleases / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D015335:Molecular Probes / Q000737:chemistry*; D040081:Protein Array Analysis; D011799:Quinazolines / Q000737:chemistry*; D039381:RNA Cap-Binding Proteins / Q000032:analysis*; D012333:RNA, Messenger / Q000235:genetics; D055540:Survival of Motor Neuron 2 Protein / Q000032:analysis; D014316:Tritium
chemical_list: D015335:Molecular Probes; C000623384:PF-06652474; D011799:Quinazolines; D039381:RNA Cap-Binding Proteins; D012333:RNA, Messenger; C526477:SMN2 protein, human; D055540:Survival of Motor Neuron 2 Protein; D014316:Tritium; D004722:Endoribonucleases; C485332:DcpS protein, human
keywords: affinity enrichment; cap-binding protein; chemical probe; protein microarray