D. Zanini et R. Roy, CHEMOENZYMATIC SYNTHESIS AND LECTIN-BINDING PROPERTIES OF DENDRITIC N-ACETYLLACTOSAMINE, Bioconjugate chemistry, 8(2), 1997, pp. 187-192
Proof that multivalency amplifies individual carbohydrate-protein inte
ractions is growing. N-Acetylglucosamine (GlcNAc)-based dendrimers wit
h valencies of two (9), four (10), and eight (11) were prepared in fai
r to excellent yields (65-99%) on the basis of the rational scaffoldin
g of L-lysine on solid phase using established Fmoc and HOBt chemistry
. These GlcNAc dendrimers were then further transformed enzymatically
(79-90% yields) into dendritic N-acetyllactosamine (LacNAc) derivative
s [di- (12), tetra- (13), and octavalent (14)] using UDPglucose, UDP-g
lucose 4'-epimerase, and GlcNAc beta-1,4-galactosyltransferase. GlcNAc
and LacNAc dendrimers were used to inhibit lectin-porcine stomach muc
in interactions. Wheat germ agglutinin and Erythrina cristagalli lecti
n were used for GlcNAc and LacNAc dendrimers, respectively. Di-, tetra
-, and octavalent GlcNAc dendrimers exhibited IC(50)s of 3100, 509, an
d 88 mu M (6200, 2040, and 703 mu M, with respect to monomeric GlcNAc
content). IC(50)s for the LacNAc series were 341, 143, and 86 mu M (68
2, 574, and 692 mu M, as compared with monomeric LacNAc content). Thes
e data represent more than 20-fold increases in inhibitory potential f
or dendritic GlcNAc as compared to that for monomeric GlcNAc. Studies
with E. cristagalli do not reveal significant increased inhibitory pot
ential with multivalency.