Identification and characterization of inhibitory nanobody against p38δ.

Biochem Biophys Res Commun

Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China; Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Sichuan, 610041, China. Electronic address:

Published: April 2022

p38δ is a member of p38 mitogen-activated protein kinases (MAPKs) family that displays cell- and tissue-specific expression patterns. Recent studies demonstrate that p38δ is centrally involved in several pathologic events, such as diabetes, neurodegeneration diseases, inflammatory diseases, and cancer, and suggest that it may be a potential target for diagnosis and therapy of specific diseases. A nanobody is a new type of antibody that exhibits high antigen-binding activity, solubility, stability, and easy production. This study utilized phage display to isolate nanobodies specifically against p38δ from a fully synthetic nanobody library. Two of them, nanobodies Nb13-6 and Nb13-1, display high binding activity to p38δ, less cross-reactivity with other p38 MAPKs, and high thermal and pH stabilities. Modeling and docking analysis indicated that Nb13-6 is mostly linked to the activation loop of p38δ. Furthermore, detailed studies revealed that Nb13-6 inhibited the protein kinase activity of p38δ and the growth of cancer cells. Therefore, this study provides p38δ-specific nanobodies that are promisingly exploited for diagnosing and treating p38δ-associated diseases.

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http://dx.doi.org/10.1016/j.bbrc.2022.01.080DOI Listing

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