The molecular recognition features of a glycomimetic ( 9‐Ad‐6SL ), selective toward Siglec‐10, a sialic acid‐binding immunoglobulin‐like lectin involved in immune regulation, have been unraveled using a combination of experimental NMR methods and computational chemistry protocols. Given the presence of two arginine residues within the shallow binding site—canonical R119 and noncanonical R127—both of which engage the carboxyl group of sialic acid, the interaction of the glycomimetic with the corresponding Arg‐to‐Ala mutants (R119A, R127A) of Siglec‐10 has also been evaluated. The obtained results demonstrate that, at least for Siglec‐10, the presence of large hydrophobic groups in the glycomimetic strongly influences the molecular recognition process. In addition, these findings reveal the intricacy for establishing a rational structure‐based ligand design for Siglec‐10 with the potential to be used for therapeutic targeting in cancer immunotherapy.
Valverde et al. (Sun,) studied this question.