L-N-6-(1-IMINOETHYL)LYSINE - A SELECTIVE INHIBITOR OF INDUCIBLE NITRIC-OXIDE SYNTHASE

L-N-6-(1-Iminoethyl)lysine (L-NIL) has been synthesized and is shown t o be both a potent and selective inhibitor of mouse inducible nitric o xide synthase (miNOS). L-NIL has an IC50 of 3.3 mu M for miNOS compare d to an IC50 of 92 mu M for rat brain constitutive NO indicating that L-NIL is 28-fold more selective for inducible NOS. L-N-5-(1-Iminoethyl )ornithine (L-NIO), which differs from L-NIL by having one less methyl ene group, has very similar potency for inducible NOS, but lacks selec tivity. DL-N-7-(1-Iminoethyl)homolysine was also synthesized and found to be substantially less potent than L-NIL or L-NIO, with intermediat e selectivity for inducible NOS, These data suggest that L-NIL may be useful as a selective inhibitor of inducible NOS for determining the r ole of this enzyme in disease models.