Competitive SPR using an intracellular anti-LMO2 antibody identifies novel LMO2-interacting compounds.
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Date
2021-03-29Author
Canning, P
Bataille, C
Bery, N
Milhas, S
Hayes, A
Raynaud, F
Miller, A
Rabbitts, T
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Research team
Chromosomal Translocations and Intracellular Antibody Therapeutics
Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
Chromosomal Translocations and Intracellular Antibody Therapeutics
Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
Language
eng
Date accepted
2021-03-26
License start date
2021-03-29
Citation
Journal of immunological methods, 2021, 494 pp. 113051 - ?
Publisher
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