A conformation-selective monoclonal antibody against a small molecule-stabilised signalling-deficient form of TNF.

ABSTRACT: We have recently described the development of a series of small-molecule inhibitors of human tumour necrosis factor (TNF) that stabilise an open, asymmetric, signalling-deficient form of the soluble TNF trimer. Here, we describe the generation, characterisation, and utility of a monoclonal antibody that selectively binds with high affinity to the asymmetric TNF trimer-small molecule complex. The antibody helps to define the molecular dynamics of the apo TNF trimer, reveals the mode of action and specificity of the small molecule inhibitors, acts as a chaperone in solving the human TNF-TNFR1 complex crystal structure, and facilitates the measurement of small molecule target occupancy in complex biological samples. We believe this work defines a role for monoclonal antibodies as tools to fac

SUBMITTER: Lightwood DJ 

PROVIDER: S-EPMC7835358 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature