Competitive SPR using an intracellular anti-LMO2 antibody identifies novel LMO2-interacting compounds.
Adaptor Proteins, Signal Transducing
/ metabolism
Antibodies
/ metabolism
Antigens, Neoplasm
/ metabolism
Binding, Competitive
Cells, Cultured
Drug Discovery
Humans
Immunoglobulin Fragments
/ genetics
Intracellular Space
LIM Domain Proteins
/ metabolism
Leukemia, T-Cell
/ metabolism
Protein Conformation
Proto-Oncogene Proteins
/ metabolism
Small Molecule Libraries
Surface Plasmon Resonance
T-Cell Acute Lymphocytic Leukemia Protein 1
/ metabolism
T-Lymphocytes
/ immunology
Abd compounds
Chromosomal translocations
Drug discovery
GATA
Intracellular antibodies
LMO2
Leukaemia
SPR
TAL1/SCL
Journal
Journal of immunological methods
ISSN: 1872-7905
Titre abrégé: J Immunol Methods
Pays: Netherlands
ID NLM: 1305440
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
11
12
2020
revised:
10
03
2021
accepted:
26
03
2021
pubmed:
2
4
2021
medline:
25
2
2023
entrez:
1
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33794223
pii: S0022-1759(21)00096-X
doi: 10.1016/j.jim.2021.113051
pmc: PMC8208243
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Antibodies
0
Antigens, Neoplasm
0
Immunoglobulin Fragments
0
LIM Domain Proteins
0
LMO2 protein, human
0
Proto-Oncogene Proteins
0
Small Molecule Libraries
0
T-Cell Acute Lymphocytic Leukemia Protein 1
0
TAL1 protein, human
135471-20-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113051Subventions
Organisme : Medical Research Council
ID : MR/J000612/1
Pays : United Kingdom
Informations de copyright
Copyright © 2021. Published by Elsevier B.V.
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