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

Calreticulin (CRT) is a multifunctional lectin involved in glycoprotein quality control and immune-associated cell surface signaling and has recently attracted attention as a potential molecular target in cancer-associated stress responses, including immunogenic cell death. We report the design and synthesis of a novel CRT-targeting trisaccharide (α-D-Glcp-(1 → 3)-α-D-Manp-(1 → 2)-Man, G1M2), G1M2-EG8-ZnChl, in which a CRT-recognizing trisaccharide is covalently linked to a zinc chlorophyll derivative (ZnChl) as a photosensitizer through an oligoethylene glycol spacer. The conjugate exhibited characteristic chlorin absorption bands at approximately 434 and 666 nm in aqueous buffer, enabling excitation in the red-light region. Upon light irradiation, singlet oxygen generation was confirmed using 1,3-diphenylisobenzofuran as a chemical quencher in ethanol, and the singlet oxygen quantum yield was determined to be Φ_Δ = 0.26. The complex showed negligible photodegradation under the irradiation for 80 s, indicating sufficient photostability of the chlorin core in G1M2-EG8-ZnChl. Binding assays demonstrated that G1M2-EG8-ZnChl interacted with human CRT through its glycan recognition domain and aglycon recognition domain. Although further biological investigations are required to elucidate cellular interactions and functional outcomes, this work demonstrates a molecular design strategy for integrating CRT-recognition motifs with photosensitizers while retaining essential photophysical and photochemical properties.