Epitope mapping of an anti-FSH antibody

Wichita State University has developed an anti-folliculo stimulating hormone (FSH) antibody having higher affinity for a specific glycosylated isoform of the FSH. MAbSilico determined and experimentally validated the epitope.

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Technology
Antibody characterization
Tools used
Epitope mapping
Target structural modeling

The anti-FSH antibody was docked on the 3D structure of the FSH, and the epitope predicted. Experimental validation was tricky, since FSH is not a membrane protein, and is a notoriously difficult protein to produce. Indeed, FSH is constituted of two chains (⍺ and ß), assembled and linked by disulfide bonds. To validate the epitope prediction, a construct was designed, including the two chains fused to a trans-membrane helix domain, resulting in the membrane anchorage of the hormone. We validated that the antibody binds with high affinity to this construct. Mutations were then introduced at the positions predicted to belong to the epitope of the antibody. We showed experimentally that binding to the mutants was decreased or abolished, validating our predictions.

Results were presented at the conference “Writing the Future of Drug Discovery”.