The use of intracellular antibodies as templates to derive surrogate compounds is an important objective because intracellular antibodies can be employed initially for target validation in pre-clinical assays and subsequently employed in compound library screens. LMO2 is a T cell oncogenic protein activated in the majority of T cell acute leukaemias. We have used an inhibitory intracellular antibody fragment as a competitor in a small molecule library screen using competitive surface plasmon resonance (cSPR) to identify compounds that bind to LMO2. We selected four compounds that bind to LMO2 but not when the anti-LMO2 intracellular antibody fragment is bound to it. These findings further illustrate the value of intracellular antibodies in the initial stages of drug discovery campaigns and more generally antibodies, or antibody fragments, can be the starting point for chemical compound development as surrogates of the antibody combining site.
Journal article
2021-07-01T00:00:00+00:00
494
Abd compounds, Chromosomal translocations, Drug discovery, GATA, Intracellular antibodies, LMO2, Leukaemia, SPR, TAL1/SCL, Adaptor Proteins, Signal Transducing, Antibodies, Antigens, Neoplasm, Binding, Competitive, Cells, Cultured, Drug Discovery, Humans, Immunoglobulin Fragments, Intracellular Space, LIM Domain Proteins, Leukemia, T-Cell, Protein Conformation, Proto-Oncogene Proteins, Small Molecule Libraries, Surface Plasmon Resonance, T-Cell Acute Lymphocytic Leukemia Protein 1, T-Lymphocytes