Related Experiment Video
Updated: Oct 2, 2025
Selection of Transporter-Targeted Inhibitory Nanobodies by Solid-Supported-Membrane SSM-Based Electrophysiology
Published on: May 3, 2021
Identification and characterization of inhibitory nanobody against p38δ
Chenliang Zhang1, Qiulin Tang1, Hongwei Xia1
1Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Abstract:
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.
Insights
Researchers developed specific nanobodies targeting p38δ, a protein kinase implicated in diseases like cancer and diabetes. These nanobodies show potential for diagnosing and treating p38δ-related conditions.
Area of Science:
- Molecular Biology
- Immunology
- Biochemistry
Background:
- p38δ, a p38 mitogen-activated protein kinase (MAPK), exhibits specific expression and is implicated in diseases including diabetes, neurodegeneration, inflammation, and cancer.
- p38δ represents a potential therapeutic and diagnostic target due to its role in various pathologies.
- Nanobodies, derived from single-domain antibody fragments, offer advantages in antigen binding, stability, solubility, and production.
Purpose of the Study:
- To isolate and characterize novel nanobodies with high specificity and affinity for p38δ.
- To evaluate the therapeutic potential of these nanobodies in inhibiting p38δ activity and related cellular processes.
Main Methods:
- Phage display technology was employed to screen a synthetic nanobody library for binders against p38δ.
- Selected nanobodies (Nb13-6 and Nb13-1) were assessed for binding affinity, cross-reactivity with other p38 MAPKs, and stability under varying thermal and pH conditions.
- Structural modeling and docking analyses were performed to understand nanobody-p38δ interactions.
- The functional impact of Nb13-6 on p38δ kinase activity and cancer cell proliferation was investigated.
Main Results:
- Two nanobodies, Nb13-6 and Nb13-1, were identified with high binding activity to p38δ.
- These nanobodies demonstrated reduced cross-reactivity with other p38 MAPK family members and exhibited excellent thermal and pH stability.
- Nb13-6 was found to bind to the activation loop of p38δ.
- Nb13-6 effectively inhibited p38δ protein kinase activity and suppressed the growth of cancer cells.
Conclusions:
- p38δ-specific nanobodies, particularly Nb13-6, have been successfully developed.
- These nanobodies possess desirable characteristics for potential diagnostic and therapeutic applications.
- The findings support the utility of p38δ-specific nanobodies in addressing p38δ-associated diseases.
