Ot. Keppler et al., BIOSYNTHETIC MODULATION OF SIALIC ACID-DEPENDENT VIRUS-RECEPTOR INTERACTIONS OF 2 PRIMATE POLYOMA VIRUSES, The Journal of biological chemistry, 270(3), 1995, pp. 1308-1314
Sialic acids are essential components of the cell surface receptors of
many microorganisms including viruses, A synthetic, N-substituted D-m
annosamine derivative has been shown to act as precursor for structura
lly altered sialic acid incorporated into glycoconjugates in vivo (Kay
ser, H., Zeitler, R., Kannicht, C., Grunow, D., Nuck, R., and Reutter,
W. (1992) J. Biol. Chem. 267, 16934-16938). In this study we have ana
lyzed the potential of three different sialic acid precursor analogues
to modulate sialic acid-dependent virus receptor function on differen
t cells, We show that treatment with these D-mannosamine derivatives c
an result in the structural modification of about 50% of total cellula
r sialic acid content, Treatment interfered drastically and specifical
ly with sialic acid-dependent infection of two distinct primate polyom
a viruses, Both inhibition (over 95%) and enhancement (up to 7-fold) o
f virus binding and infection were observed depending on the N-acyl su
bstitution at the C-5 position of sialic acid, These effects were attr
ibuted to the synthesis of metabolically modified, sialylated virus re
ceptors, carrying elongated N-acyl groups, with altered binding affini
ties for virus particles, Thus, the principle of biosynthetic modifica
tion of sialic acid by application of appropriate sialic acid precurso
rs to tissue culture or in vivo offers new means to specifically influ
ence sialic acid-dependent ligand-receptor interactions and could be a
potent tool to further clarify the biological functions of sialic aci
d, in particular its N-acyl side chain.