title: Progress in discovery of small-molecule modulators of protein-protein interactions via fragment screening.
abstract: Protein-protein interactions (PPIs) present a formidable challenge to medicinal chemistry. The extended and open nature of many binding sites at protein interfaces has made it difficult to find useful chemical matter by traditional screening methods using standard screening libraries. This Digest focuses on the progress that has been made in discovering small-molecule modulators for a diverse selection of PPI targets using fragment screening and highlights the utility of this strategy in this context.
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Inc, 610 Main Street, Cambridge, MA 02139, USA. Electronic address: thomas.v.magee@pfizer.com.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Magee
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D056004:Molecular Dynamics Simulation; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D011506:Proteins; D054852:Small Molecule Libraries
keywords: Fragments; PPI