These data indicate that the turn-on of keto emission is likely not due to nonspecific binding to TTR, but instead indicates specific binding in the designed A108G pocket wherein the protein increases the efficiency of emission via the keto versus the enol channel. Unfortunately, all other derivatives (3, 4, 6-8, Scheme 1) did not exhibit a change in emission between buffer, WT TTR□ and A108G TTR■ tetramers (Fig. ). It is important to recognize, however, that a lack of a change in the emission signal does not inform on the ability of a given molecule to bind the TTR binding pocket. It is possible that derivatives 3, 4, and 6-8, may bind the TTR pocket with high affinity, but the protein is unable to increase the efficiency of emission.