title: Design and Synthesis of Biaryl DNA-Encoded Libraries.
abstract: DNA-encoded library technology (ELT) is a powerful tool for the discovery of new small-molecule ligands to various protein targets. Here we report the design and synthesis of biaryl DNA-encoded libraries based on the scaffold of 5-formyl 3-iodobenzoic acid. Three reactions on DNA template, acylation, Suzuki-Miyaura coupling and reductive amination, were applied in the library synthesis. The three cycle library of 3.5 million diversity has delivered potent hits for phosphoinositide 3-kinase α (PI3Kα).
authors: GlaxoSmithKline , Platform Technology & Science, ELT-Boston, 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors: Yun
authors: Y
authors: Ding
authors: GlaxoSmithKline , Platform Technology & Science, ELT-Boston, 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors: G Joseph
authors: GJ
authors: Franklin
authors: GlaxoSmithKline , Platform Technology & Science, ELT-Boston, 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors: Jennifer L
authors: JL
authors: DeLorey
authors: GlaxoSmithKline , Platform Technology & Science, ELT-Boston, 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors: Paolo A
authors: PA
authors: Centrella
authors: GlaxoSmithKline , Platform Technology & Science, ELT-Boston, 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors: Sibongile
authors: S
authors: Mataruse
authors: GlaxoSmithKline , Platform Technology & Science, ELT-Boston, 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors: Matthew A
authors: MA
authors: Clark
authors: GlaxoSmithKline , Platform Technology & Science, ELT-Boston, 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors: Steven R
authors: SR
authors: Skinner
authors: GlaxoSmithKline , Platform Technology & Science, ELT-Boston, 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors: Svetlana
authors: S
authors: Belyanskaya
mesh_terms: D000215:Acylation; D000586:Amination; D020650:Combinatorial Chemistry Techniques; D004247:DNA / Q000737:chemistry*; D006801:Humans; D007463:Iodobenzoates / Q000737:chemistry*; D008024:Ligands; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
chemical_list: D007463:Iodobenzoates; D008024:Ligands; D054852:Small Molecule Libraries; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases
keywords: DNA-encoded library technology; Suzuki−Miyaura cross-coupling