Calreticulin-targeting trisaccharide Glc-Man-Man ligand conjugated with zinc chlorophyll derivative as a photosensitizer

We report the design and synthesis of a novel calreticulin (CRT)-targeting trisaccharide (Glucoseα1-3Mannoseα1-2Mannose, G1M2 ) ligand, G1M2-EG8-ZnChl , bearing a zinc chlorophyll derivative ( ZnChl ) as a photosensitizer. The ligand was constructed by conjugating the CRT-recognizing trisaccharide to the chlorophyll moiety via a glycine and an oligoethylene glycol linker ( EG8 ). G1M2-EG8-ZnChl exhibited monomeric behavior without aggregation in both ethanol and aqueous 3-( N -morpholino)propanesulfonic acid buffer, as confirmed by ultraviolet–visible absorption spectral and dynamic light scattering measurements. Upon red light irradiation, the ligand generated singlet oxygen efficiently without significant photodegradation. Binding assays demonstrated that G1M2-EG8-ZnChl interacted with human CRT through its glycan recognition domain and aglycon recognition domain. The G1M2-EG8-ZnChl may be useful as a probe showing dual functions such as CRT-binding ability and photo-functionality.