The synthesis and enzymatic hydrolysis of poly-D-lysine.

In studies of the inhibition in viva of animal viruses by poly-n-lysine, Rubini et al. (1) and Green et al. (2-4) obtained data which suggested that poly-L-lysine is hydrolyzed by the proteolytic enzymes of the allantoic fluid, and that this enzymatic hydrolysis may limit its biological activity. The enzymatic hydrolysis of poly-n-lysine was reported by Katchalski (5) and by Waley and Watson (6). Since D peptides are generally more resistant to enzymatic hydrolysis than their L isomers, poly-n-lysine was synthesized and tested for antiviral activity. However, the results showed comparable activity for both optical isomers and suggested that the polyn-lysine is hydrolyzed or metabolized almost as rapidly as the corresponding L polypeptide (7). In view of these unexpected results, it was of interest to compare the susceptibility to hydrolysis of poly-Land poly-Dlysine by different proteolytic enzyme preparations. The resolution of nn-lysine hydrochloride was first reported in 1936 by Berg (8), who employed fractional crystallization of the camphorate in 50 per cent methanol. In 1948, Borsook et al. (9) obtained n-lysine hydrochloride by the enzymatic synthesis of the anilide of dicarbobenzoxy-n-lysine with papain. Greenstein and associates (10) in 1950 obtained D-lysine hydrochloride and used hog kidney enzyme to hydrolyze selectively the dichloroacetyl derivative of L-lysine. For the present work, n-lysine hydrochloride was obtained by the enzymatic synthesis of the anilide of diisobutyryl-n-lysine with papain as reported by Doherty and Popenoe (11) with modifications.