Lectins-glycoconjugates interactions: Experimental and computational docking studies of the binding and agglutination of eight different lectins in a comparative manner

Altering the lectin properties by chemically synthesized glycoconjugates is important in glycobiology. A series of eight plant lectins with varying carbohydrate specificity were chosen as model systems to study the binding by synthetic glycoconjugates. One of our earlier paper deals with the binding of glycoconjugates by jacalin. Further to this, we have now extended the studies to several other lectins having specificities towards glucose/mannose, galactose and lactose, and the results are reported in this paper on a comparative manner. The binding aspects were established by hemagglutination and fluorescence spectroscopy, and the conformational changes by CD spectroscopy. Out of the fourteen glycoconjugates used in the present study, a galactosyl naphthyl derivative, 1c turns out to be most effective towards galactose specific lectin in agglutination inhibition, fluorescence quenching by inducing considerable conformational changes. Similarly, mannosyl-naphthyl derivative, 3c turns out to be most effective in inhibiting the agglutination of Glc/Man specific lectins. Present study demonstrates differential recognition of conjugates towards lectins. The results also supported the existence of a correlation between the glycoconjugate and lectin specificity at the carbohydrate recognition domain (CRD). The glycoconjugate that inhibits the agglutination binds in the CRD via polar interactions as well as by nonpolar/hydrophobic interactions arising from the aromatic moiety of the conjugate, whereas, the non inhibiting conjugates bind primarily via hydrophobic interactions. The specific and selective binding of the glycoconjugates by these lectins were proven by the docking studies. Thus, the present study has contributed immensely towards understanding the molecular interactions present between the lectins and small molecules that will eventually help better drug design where the presence of hydrophobic moieties would play an important role.