Hydrophobic interactions are involved in the inhibition of human leukocyte elastase by alkyltrimethylammonium salts.

Electrostatic forces and hydrophobic interactions had been suggested to modify the adsorption of elastases onto insoluble fibrous elastin, which is the initial stage of elastolysis, but conflicting results had been obtained, and comparison between compounds with different structures was difficult. In order to explore these observations, we have studied the effect of six alkyltrimethylammonium bromides, with alkyl chain length ranging from six to 16 carbon atoms, on human leucocyte elastase activities, either with a synthetic substrate or with insoluble elastin. The enzymatic studies were performed either spectrophotometrically or using conductimetry, and direct binding on to elastin was conductimetrically measured. Binding of the alkyltrimethylammonium salts is increasing with alkyl chain length and we could demonstrate a cooperative binding for tetra- and hexadecyl chains. No effect of the six compounds could be evidenced on hydrolysis of a specific synthetic substrate. With insoluble elastin, elastolysis inhibition could be demonstrated for alkyl chain longer than ten carbon atoms, the effect increasing with chain length. A similar inhibition was observed with the soluble kappa-elastin, but it was less effective. The study shows that the interaction between the alkyltrimethylammonium salts and elastin plays a major role in the inhibitory potency of these molecules. As this effect is enhanced with alkyl chain length, it was concluded that hydrophobic interactions favour their binding, protecting elastin against elastase adsorption.