Selective Coupling of Aminophosphole-Based Fluorophores to Unprotected Peptides through P-S Bond Formation

Phosphole-based fluorophores are attractive dyes for bioimaging due to their relatively compact molecular structures, strong fluorescence up to the near-infrared region with large Stokes shifts, and remarkable resistance to photobleaching. Therefore, the development of efficient and chemoselective coupling methods for functionalizing phospholes is of significant interest for biomolecular labeling. Herein, we describe the synthesis of novel P-aminophospholes and their use for direct conjugation to cysteinyl peptides under mild conditions. The utility of this approach was demonstrated by successfully labeling the bioactive peptide ghrelin(1,8)-Cys9, as well as the growth hormone secretagogue receptor, without affecting its biological activity.