Sialic acid and sialyl‐lactose glyco‐conjugates: design, synthesis and binding assays to lectins and swine influenza H1N1 virus

Abstract

The terminal parts of the influenza hemagglutinin (HA) receptors α2,6- and α2,3-sialyllactoses were conjugated to an artificial carrier, named sequential oligopeptide carrier (SOC(4) ), to formulate human and avian receptor mimics, respectively. SOC(4) , formed by the tripeptide unit Lys-Aib-Gly, adopts a rigid helicoids-type conformation, which enables the conjugation of biomolecules to the Lys-N(ε) H(2) groups. By doing so, it preserves their initial conformations and functionalities of the epitopes. We report that SOC(4) -glyco-conjugate bearing two copies of the α2,6-sialyllactose is specifically recognized by the biotinylated Sambucus nigra (elderberry) bark lectin, which binds preferentially to sialic acid in an α2,6-linkage. SOC(4) -glyco-conjugate bearing two copies of the α2,3-sialyllactose was not recognized by the biotinylated Maackia amurensis lectin, despite its well-known α2,3-sialyl bond specificity. However, preliminary immune blot assays showed that H1N1 virus binds to both the SOC(4) -glyco-conjugates immobilized onto nitrocellulose membrane. It is concluded that Ac-SOC(4) [(Ac)(2) ,(3'SL-Aoa)(2) ]-NH(2) 5 and Ac-SOC(4) [(Ac)(2) ,(6'SL-Aoa)(2) ]-NH(2) 6 mimic the HA receptors. These findings could be useful for easy screening of binding and inhibition assays of virus-receptor interactions.

Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas, and Pharmacology

“…It has been concluded that HMO at or below the level found in breast milk increases innate immunity to respiratory viruses in vitro and can affect innate immunity. As a result of blocking hemagglutination of influenza viruses, immobilized 3 SL and 6 SL attachments prevent infectivity of influenza viruses [60,61]. A number of external HMO connections have been identified that bind to influenza virus [60,61].…”

“…As a result of blocking hemagglutination of influenza viruses, immobilized 3 SL and 6 SL attachments prevent infectivity of influenza viruses [60,61]. A number of external HMO connections have been identified that bind to influenza virus [60,61]. A number of additional sialic acids containing HMO that bind to influenza virus have also been identified.…”

Immunological Effects of Human Milk Oligosaccharides

“…Immobilized 3′SL and 6′SL haven been shown to prevent infectivity of influenza viruses as a result of blocking the haemagglutins of influenza viruses ( 112 , 113 ), and Yu et al identified a number of additional sialic acid containing HMOs that bind to influenza virus ( 114 ). The effects of these HMOs was confirmed in a functional infection assay in vitro , where 6′SL and LNnT were shown to reduce the viral load of influenza in airway epithelial cells, and 2′FL did the same for respiratory syncytial virus (RSV) ( 92 ).…”

Gold standard for nutrition: a review of human milk oligosaccharide and its effects on infant gut microbiota

“…In addition to preventing the gut virus, HMOs also can inhibit respiratory virus infections [ 161 ]. 2′-FL has been shown to reduce viral load of respiratory syncytial virus [ 162 ].…”