Catch, Cut, or Block? Versatile 4‐‐Derivatized Sialyl Glycosides for Influenza Virus Neuraminidase Detection and Purification
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Abstract Seasonal influenza continues to threaten human lives and pose a significant burden to healthcare systems and the economy, emphasizing the need for developing better influenza vaccines, diagnostics, and antiviral therapeutics. To address these challenges, we generated a library of structurally diverse sialyl glycosides containing 4‐‐derivatized sialic acids by a highly efficient one‐pot two‐enzyme chemoenzymatic sialylation strategy. Sialosides containing 4‐azido‐substituted sialic acid were selectively cleaved by sialidases from influenza viruses, whereas sialosides containing 4‐acetamido‐modified sialic acid were resistant to sialidase cleavage. Interestingly, sialosides containing 4‐amino‐ or 4‐guanidino‐substituted sialic acid were effective inhibitors moderately or highly resistant to cleavage by influenza sialidases (also called neuraminidases). The sialosides containing the 4‐guanidino‐substituted sialic acid represent a new class of sialidase substrate analog‐based inhibitors. We took advantage of this unique property to create a ligand‐based approach for efficiently isolating influenza virions from egg allantoic fluid with high purity. Together, these compounds are versatile probes and ligands for developing new approaches to detect, profile, isolate, and characterize influenza viruses via neuraminidases on their surface. Sialyl glycosides containing 4‐‐derivatized sialic acids synthesized by a highly efficient one‐pot two‐enzyme (OP2E) chemoenzymatic sialyla
Abstract
Abstract Seasonal influenza continues to threaten human lives and pose a significant burden to healthcare systems and the economy, emphasizing the need for developing better influenza vaccines, diagnostics, and antiviral therapeutics. To address these challenges, we generated a library of structurally diverse sialyl glycosides containing 4‐‐derivatized sialic acids by a highly efficient one‐pot two‐enzyme chemoenzymatic sialylation strategy. Sialosides containing 4‐azido‐substituted sialic acid were selectively cleaved by sialidases from influenza viruses, whereas sialosides containing 4‐acetamido‐modified sialic acid were resistant to sialidase cleavage. Interestingly, sialosides containing 4‐amino‐ or 4‐guanidino‐substituted sialic acid were effective inhibitors moderately or highly resistant to cleavage by influenza sialidases (also called neuraminidases). The sialosides containing the 4‐guanidino‐substituted sialic acid represent a new class of sialidase substrate analog‐based inhibitors. We took advantage of this unique property to create a ligand‐based approach for efficiently isolating influenza virions from egg allantoic fluid with high purity. Together, these compounds are versatile probes and ligands for developing new approaches to detect, profile, isolate, and characterize influenza viruses via neuraminidases on their surface. Sialyl glycosides containing 4‐‐derivatized sialic acids synthesized by a highly efficient one‐pot two‐enzyme (OP2E) chemoenzymatic sialylation strategy have been shown to be versatile probes. They can resist sialidase cleavage, be selective substrates by influenza sialidases, or be nanomolar substrate analog‐based inhibitors and affinity ligands selectively for influenza sialidases. Beads immobilized with 4‐guanidino‐sialosides have been demonstrated for purifying influenza virions. anie202505903-abs-0001 graphical