Shape Shifting Supramolecule

Supramolecule that Changes Its Structure on Binding with Receptor Molecule

A novel strategy for the inhibition of influenza virus infection by disrupting the receptor functions was proposed and described.  A polymeric inhibitor that contains lyso GM3 ganglioside was synthesized as amphiphilic polymer with receptor specific ligands.

9-Fluorenylmethyloxylcarbonyl (Fmoc) protected (ε-amino group) L-lysine was attached with the fluorescent tag BODIPY, which was then coupled with lyso GM3 ganglioside to yield a fluorescent GM3 analog. Removal of the Fmoc group followed by amide formation with activated poly-L-glutamic acid (PGA) provided lyso GM3-PGA containing the BODIPY fluorophore. The lyso GM3 content was calculated from the u.v. absorption of the fluorophore to be 3 mol %. Because of the amphiphilic nature, the polymer was shown to have folded structure in aqueous media. The inhibitory activities of lyso GM3-PGA, lyso GM3, and GM3 oligosaccharide (sialyl lactose) against the binding of influenza A/PR/8/34 (H1N1) were investigated using an ELISA assay. The IC50 values for the polymeric inhibitor, GM3, lyso GM3, and sialyllactose were 7.5 x 10-12, 1.0 x 10-9, 3.0 x 10-9, and 1.5 x 10-7 molar, respectively, based on monomeric sialic acid. PGA showed no inhibition against the influenza.

Furthermore, later we discovered the type of polymer ligand-type inhibitor synergistically inhibits influenza virus infection together with zanamivir and oseltamivir, thus is considered as a new potential candidate for influenza control and for use in combination with NAI drugs for minimizing toxicity, delayed development of resistance.

Although we did not stress the polymer was found to inhibit both HA and NA. This effect was considered due to a part of the steric stabilization of a viral particle by this polymer. We postulate a mechanism to the polymer backbone interferes the NA reaction as the polymer rap around the virus.

Reference

Lyso GM3 ganglioside-poly-L-glutamic acid conjugate as inhibitor of influenza hemagglutinin. Kamitakahara, H. Kanie, O. Wong, C,-H. Angew. Chem. Int. Ed., 1998, 37, 1524-1528.

6SLN-lipo PGA specifically catches (coats) human influenza virus and synergizes neuraminidase-targeting drugs for human influenza therapeutic potential. Sriwilaijaroen, N. et al. J. Antimicrob. Chemother., 2015, 70, 2797-2809.

 

Comments are closed.