FlAsH-tetracysteine complexes

The four arsenic-sulfur bonds present in the FlAsH-tetracysteine complex rigidly lock the fluorophore to the peptide so that any rotational motion reflects that of the peptide or protein rather than the dye. This is in direct contrast to conventional coupling chemistries used to modify proteins in which the fluorophore is attached by a rotatable single bond to the flexible side chain of an amino acid. 

Confirmation of the increased affinity of FlAsH for the motif CCPGCC came from detailed kinetic studies of the on- and off-rates for the complexes [8], The reaction of FlAsH-EDT2 with tetracysteines involves at least two steps, as each EDT has to dissociate before binding the cysteines. To simplify the reaction, we looked at the reaction of FlAsH lacking EDT in which the arsenics are present as arsenoxides (Scheme 8.1-2). Reaction of FlAsH... 

Figure 4.25 Biarsenical ligands. Synthesis of Flash EDT2 and proposed structure of its complex with an a-helical tetracysteine-containing peptide or protein domain. The structure is drawn with the i and i +4 thiols bridged by one arsenic and the / + 1 and / + 5 thiols bridged by the other (Reproduced from Griffin et al., 1998, Fig. 1).

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