title: A library approach to rapidly discover photoaffinity probes of the mRNA decapping scavenger enzyme DcpS.
abstract: Despite its diverse applications, such as identification of the protein binding partners of small molecules and investigation of intracellular drug-target engagement, photoaffinity labelling (PAL) is intrinsically challenging, primarily due to the difficulty in discovering functionally active photoaffinity probes. Here we describe the creation of a chemoproteomic library to discover a novel photoaffinity probe for DcpS, an mRNA decapping enzyme that is a putative target for Spinal Muscular Atrophy. This library approach expedites the discovery of photoaffinity probes and expands the chemical biology toolbox to include RNA cap-binding proteins.
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Inc., 610 Main Street, Cambridge, MA 02139, USA. Hua.Xu@pfizer.com Lyn.Jones@pfizer.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Erik C
authors.initials: EC
authors.lastname: Hett
authors.forename: Ariamala
authors.initials: A
authors.lastname: Gopalsamy
authors.forename: Mihir D
authors.initials: MD
authors.lastname: Parikh
authors.forename: Kieran F
authors.initials: KF
authors.lastname: Geoghegan
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kyne
authors.forename: Carol A
authors.initials: CA
authors.lastname: Menard
authors.forename: Arjun
authors.initials: A
authors.lastname: Narayanan
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Robinson
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Johnson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tones
authors.forename: Lyn H
authors.initials: LH
authors.lastname: Jones
mesh_terms: D001665:Binding Sites; D004722:Endoribonucleases / Q000737:chemistry / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D008958:Models, Molecular; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism; D019920:Photoaffinity Labels / Q000737:chemistry*; D011799:Quinazolines / Q000737:chemistry
chemical_list: D015335:Molecular Probes; D019920:Photoaffinity Labels; D011799:Quinazolines; C013474:2,4-diaminoquinazoline; D004722:Endoribonucleases; C485332:DcpS protein, human