Abstract
Abstract Glycoprotein substrates for neuraminidase and glycoprotein inhibitors of the agglutination of erythrocytes by influenza virus were subjected to oxidation by very low concentrations of periodate under conditions which selectively oxidize N-acetylneuraminic acid (NANA), to the 8carbon and 7-carbon aldehydes. Molar ratios of periodate to NANA were varied from 0.2 to 4.5. Reduction of the oxidized glycoproteins with sodium borohydride yielded glycoproteins containing the 8- and 7-carbon analogues of NANA as well as the parent 9-carbon compound in amounts depending on the quantity of periodate employed. These were quantitated in the mixture by means of gas-liquid chromatography. Under the conditions used, periodate oxidation of other sugars in the glycoproteins could not be detected. The capacity of neuraminidases from Vibrio cholerae, Clostridium perfringens, and PR-8 influenza virus to cleave N-acetylneuraminic acid or its 8-carbon (NANA-8) or 7-carbon (NANA-7) analogues from native and modified orosomucoid and from NANA-, NANA-8-, and NANA-7-N-acetylgalactosaminitol were studied. NANA-8 was hydrolyzed from the glycoproteins and the reduced disaccharide at an initial rate about 30% of that for NANA. The 7-carbon analogue of NANA was not cleaved from the reduced disaccharide, but was slowly cleaved from modified orosomucoid at an initial rate of 5 to 10% of that for NANA. It was concluded that the optimum activity of neuraminidase requires the intact structure of the polyhydroxy side chain of NANA. When the molar ratio of periodate to NANA exceeded 1.5, all of the NANA was converted to the 8- and 7-carbon analogues, and the capacity of the glycoproteins to inhibit agglutination of human erythrocytes by PR-8 influenza virus was reduced by 95 to 100%. It is concluded that carbon atoms 7, 8, and 9 in the polyhydroxy side chain of NANA acid in glycoproteins are involved in their binding to influenza virus.
Highlights
Glycoprotein substrates for neuraminidase and glycoprotein inhibitors of the agglutination of erythrocytes by influenza virus were subjected to oxidation by very low concentrations of periodate under conditions which selectively oxidize N-acetylneuraminic acid (NANA), to the 8
When the molar ratio of periodate to NANA exceeded 1.5, all of the NANA was converted to the 8- and ‘/-carbon analogues, and the capacity of the glycoproteins to inhibit agglutination of human erythrocytes by PR-8 influenza virus was reduced by 95 to 100%
It is concluded that carbon atoms 7, 8, and 9 in the polyhydroxy side chain of NANA acid in glycoproteins are involved in their binding to influenza virus
Summary
Glycoprotein substrates for neuraminidase and glycoprotein inhibitors of the agglutination of erythrocytes by influenza virus were subjected to oxidation by very low concentrations of periodate under conditions which selectively oxidize N-acetylneuraminic acid (NANA), to the 8-. When the molar ratio of periodate to NANA exceeded 1.5, all of the NANA was converted to the 8- and ‘/-carbon analogues, and the capacity of the glycoproteins to inhibit agglutination of human erythrocytes by PR-8 influenza virus was reduced by 95 to 100%. It is concluded that carbon atoms 7, 8, and 9 in the polyhydroxy side chain of NANA acid in glycoproteins are involved in their binding to influenza virus. In glycosidically bound NANA only carbon atoms 7, 8, and 9 in the polyhydroxy side chain are susceptible to periodate oxidation, it appears that these carbon atoms may be involved in some specific way in the binding of influenza virus to NANA-contain ing glycoproteins. The second part of this communication shows that three potent inhibitors of viral hemagglutination are unable to bind influenza virus when the NANA is converted to NANAand NANA-7
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