L-homoarginine studies provide insight into the antimetabolic properties of L-canavanine

A method for the chemical synthesis of L-homoarginine, based on the guanidination of L-lysine with O-methylisourea, has been developed; this procedure provides radiochemically pure L-[guanidino-C-14]homoarginine in high yield, Radiolabeled homoarginine is incorporated readily into the newly synthesized hemolymphic proteins of larvae of the tobacco hornworm, Manduca sexta without adversely affecting larval growth and development, This finding stands in sharp contrast to the effect of L-canavanine, another L-arginine analog, which is markedly deleterious to these larvae, Homoarginine is incorporated into M. sexta lysozyme, and the antibacterial proteins of the fly, Phormia terranovae with impunity, In contrast, the comparable canavanine-containing enzymes are inhibited severely, Experimental evidence is presented that the innocuous nature of homoarginine results from the elevated pK(a) value of its guanidino group which arguably exceeds even that of arginine. As a result, homoarginine does not disrupt essential residue interactions, In contrast canavanine, which is much less basic than arginine, does adversely affect R group interactions forming the requisite three-dimensional conformation of the protein, Copyright (C) 1996 Elsevier Science Ltd.