Structural and functional studies of an antibody directed against Angiopoietin-like protein 4 with interesting anti-cancer properties

• Main Author: Chua, Edmond Wei Min
• Other Authors: Tan Nguan Soon
• Format: Theses and Dissertations
• Language: English
• Published: 2015
• Subjects: DRNTU::Science::Biological sciences::Molecular biology
• Online Access: http://hdl.handle.net/10356/62057
• Institution: Nanyang Technological University

Angiopoietin-like-4 protein (ANGPTL-4) is known for its many diverse roles in both metabolic and non-metabolic processes. However, as it has no known receptors, investigation into the downstream signalling cascades initiated by ANGPTL-4 has been slow. In recent years, published research has shown its implication in various cancers, pointing to a potential therapeutic intervention, and raising the urgency to develop effective inhibitors for this multi-faceted protein. ANGPTL-4 undergoes proteolytic processing to yield 2 fragments, of which the C-terminus has been associated with regulating cancer progression., Monoclonal antibodies (11F6C4) targeting the c-terminus portion of ANGPTL-4 have been shown to arrest tumour growth in a metastatic skin tumour cell line, A-5RT3. Here, we show that a single-chain-variable fragment (ScFv) designed from the monoclonal antibody, 11F6C4, has anti-cancer properties, and can be expressed in Escherichia coli. This ScFv binds to the C-terminus portion of ANGPTL-4 and could be used for therapeutic purposes and to gain insight into important structural-related information. It would also provide a better understanding of ANGPTL-4 and its binding partners, allowing for optimized structure-based ligand design.