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aliphatic amines (Figure 1) as decarboxyl amino acid derivatives, which could mimic(Figure 2) peptide C-terminus residue. Several peptide substituted amides were efficientlysynthesized on solid-phase. As an example of usefulness this method, we present two newanalogues of our previously developed PACE4 inhibitor: Ac-LLLLRVKR-NH 2 [3].C-terminus arginine amide we replaced with substituted amines [arginine mimetics(Figure 2)]: agmatine (Agm) and 4-(aminomethyl)benzimidamide (Amba) [4] and our newinhibitors, Ac-LLLLRVK-Agm; Ac-LLLLRVK-Amba, were tested as convertase inhibitorswith improved K i in particular for PACE4 (Table 1).Table 1. Inhibitory constant [K i ] of synthesized analoguesPeptideK i [nM]against PACE4Ac-LLLLRVKR-NH 2 18.72Ac-LLLLRVK-Agm 11.77Ac-LLLLRVK-Amba 0.24The yield of the crude product from this reaction was reasonably good, however asignificant amount of brominated side products were detected. Such bromination might becaused by active bromine of NBS and maybe alternative hydrazide oxidation to diazenewith Cu (II) acetate could be used. The C-terminal modified peptides were obtained andepimerization was not noticed. Biological activity of synthesized inhibitors confirmed theirstereo chemical purity. The aryl hydrazide resin-linker is one of the most useful resins forthe synthesis of chemically C-terminally modified peptides [5] to amides, substitutedamides, nitroanilides, thioesters, acids and esters [6]. The aryl hydrazide resins were alsoused for the solid-phase head-to-tail peptide cyclization [7].AcknowledgmentsThis work is supported by research grants to RD from the Canadian Institutes of Health Research(CIHR) and the Ministère du Développement Économique, de l'Innovation et de l'Exportation(MDEIE) du Québec.References1. Kwon, Y., Welsh, K., Mitchell, A.R., Camarero, J.A. Organic Letters 6(21), 3801-3804 (2004).2. Neugebauer, W.A., Parent, A., Yuan, Xue Wen, Day, R. Adv. Exp. Med. Biol. 611, 371-372 (2009).3. Day, R., Fugère, M., Neugebauer, W.A. International patent application no. PCT/CA2009/000935;Jan 14, 2010.4. Becker, G.L., Sielaf, F., Than, M.E., Lindberg, I., Routhier, S., Day, R., Lu, Y., Garten, W.,Steinmetzer, T. J. Med. Chem. 11, 1067-1075 (2010).5. Woo, Y-H., Michell, A.R., Camarero, J.A. Int. J. of Peptide Res. and Therapeutics 13, (1-2) 181-190 (2006).6. Peters, C., Waldman, H. J. Org. Chem. 68, 6053-6055 (2003).7. Rosenbaum, C., Waldman, H. Tetrahedron Letters 42, 5677-5680 (2001).79