Role of N-methyl-8-(alkoxy)quinolinium iodide in suppression of protein–protein interactions

Abstract

There is a great deal of interest in developing small molecule inhibitors of protein misfolding and aggregation due to a growing number of pathologic states known as amyloid disorders. In searching for alternative ways to reduce protein–protein interactions or to inhibit the amyloid formation, the inhibitory effects of cationic amphiphile viz. N-methyl-8-(alkoxy)quinolinium iodide on aggregation behaviour of hen egg white lysozyme (HEWL) at alkaline pH has been studied. Even though the compounds did not protect native HEWL from conformational changes, they were effective in diminishing HEWL amyloid formation, delaying both nucleation and elongation phases. It is likely that strong binding in the HEWL compound complex, raises the activation energy barrier for protein misfolding and subsequent aggregation, thereby retarding the aggregation kinetics substantially. Cationic amphiphiles viz. N-methyl-8-(alkoxy)quinolinium iodide suppress the aggregation of HEWL. The control experiments show that the cationic head group as well as the aliphatic tail is indispensable for inhibition of aggregation process and removal of either head group or hydrocarbon chain obliterates its ability to do the same.