Mitsuaki Hirose

A chemically programmable fluorescent glycan probe dynamically switches UGGT1 activity in response to pH, establishing an active strategy to manipulate ER glycoprotein quality control.

Abstract 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 ‐Glc p ‐(1 → 3)‐α‐ D ‐Man p ‐(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.