Publications by authors named "Derrick Domingo"
Background: The near impermeability of the blood-brain barrier (BBB) and the unique neuroimmune environment of the CNS prevents the effective use of antibodies in neurological diseases. Delivery of biotherapeutics to the brain can be enabled through receptor-mediated transcytosis via proteins such as the transferrin receptor, although limitations such as the ability to use Fc-mediated effector function to clear pathogenic targets can introduce safety liabilities. Hence, novel delivery approaches with alternative clearance mechanisms are warranted.
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- Six fibronectin Type III consensus-derived Tencon domains were studied, revealing that five of them form 3D domain-swapped dimers that block their target-binding surfaces.
- The FG loop, which is crucial for stabilizing the dimer structure, varies among the variants, with insertions affecting the stability of β-turns and β-strand swapping.
- The study suggests that longer FG sequences lead to more complex structures like hexamers or helices, linking the domains' aggregation behavior in solution to their stability and potential for engineering improved versions.