L-HOMOARGININE STUDIES PROVIDE INSIGHT INTO THE ANTIMETABOLIC PROPERTIES OF L-CANAVANINE

A method for the chemical synthesis of L-homoarginine, based on the gu anidination of L-lysine with O-methylisourea, has been developed; this procedure provides radiochemically pure L-[guanidino-C-14]homoarginin e in high yield, Radiolabeled homoarginine is incorporated readily int o 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 t o these larvae, Homoarginine is incorporated into M. sexta lysozyme, a nd the antibacterial proteins of the fly, Phormia terranovae with impu nity, In contrast, the comparable canavanine-containing enzymes are in hibited severely, Experimental evidence is presented that the innocuou s nature of homoarginine results from the elevated pK(a) value of its guanidino group which arguably exceeds even that of arginine. As a res ult, homoarginine does not disrupt essential residue interactions, In contrast canavanine, which is much less basic than arginine, does adve rsely affect R group interactions forming the requisite three-dimensio nal conformation of the protein, Copyright (C) 1996 Elsevier Science L td.