(3) Because of the symmetry of the TTR homotetramer interface, however, an A108G mutation will alter both the 'top' and 'bottom' interfaces of the binding pocket (Fig. , next page). Thus, we designed the more symmetric 4 to bind both the 'top' and 'bottom' A108G TTR■ interfaces. We therefore predicted that, in free solution, 4 would be restricted to enol fluorescence. Upon specific binding to the hydrophobic binding pocket of the A108G mutant TTR■, however, keto emission would be enabled.