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ANANBIOANAL - 2010
Pharmaceutical R & D Summit
doi:10.4172/2155-9872.1000062
Interaction of Synthetic Glycoconjugates with Glycosidases and
Lectins
C.P. Rao
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, India
I
conjugates of D-galactose, D-lactose and D-ribose and C2
nhibition of the glycosidases as well as alteration of lectin properties by chemically
modified glycoconjugates can have profound effect in biology. Several C1
-imino
-imino conjugates
of D-glucose, where the nitrogen center was substituted by the salicylidene or
naphthylidene, were synthesized and characterized. Those glyco-imino-aromatic
conjugates, which are transition state analogues, exhibited 100% inhibition of
glycosidases extracted from soybean and jack bean meal. Some of these conjugates
exhibited IC50
values in the range of 20 to 50 µM and hence are potent inhibitors
of glycosidases. The kinetic studies suggested non-competitive inhibition. Similar
studies have been carried out by treating the lectins of both glucose/mannose specific
(DLL-I, pea lectin, lentil lectin), galactose specific (DLL-II, PNA, SBA, moringa
lectin) as well as lactose specific (unio lectin) with these glycoconjugates. Those
conjugates which exhibit highest glycosidase inhibition also inhibit the agglutination
of lectins and thereby modify the property of lectin accordingly. Both the experimental
and computational docking studies revealed differences in the binding strengths of
naphthylidene vs. salicylidene as well as galactosyl vs. lactosyl moieties present in
these conjugates. The differential interactions of these glyco-conjugates have been
addressed by computational docking studies to quantify the same exists between
the enzyme (Figure) or lectin and the corresponding glycoconjugate. The present
studies clearly supported the binding mainly through polar interactions in addition to
exhibiting some nonpolar/hydrophobic ones.
Docked galactosyl-naphthyl-imine conjugate with human –α-mannosidase
ANALBIOANAL-2010
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