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In an effort to investigate the use of short peptide chains as carriers of new anti-tumor agents, we synthesized four tripeptide-cytotoxic agent conjugates: DMQ-MA-Lys(DMQ-MA)-Phe -Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Ile-Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Val-Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Lys(Cbz)-Arg-Ome. The cytotoxic agent conjugated to the N-terminal and the ξ-amino group of Lysine of the tripeptide is 2,6-dimethoxyhydroquinone-3- mercaptoacetic acid (DMQ-MA). The tripeptides were synthesized by coupling protected amino acid residues according to Pfp/DCC methods (Pfp: pentafluorophenol, DCC:N,N’-dicyclohexyl- carbodiimide) in solution. Agarose gel electrophoresis showed that these compounds can cleave supercoiled DNA into open-circular form in drug concentration as low as 4-50 μM without H2O2 and UV irradiation. Further studies on their cytotoxicity for these conjugates are ongoing.
In an effort to investigate the use of short peptide chains as carriers of new anti-tumor agents, we synthesized four tripeptide-cytotoxic agent conjugates: DMQ-MA-Lys (DMQ- MA) -Phe -Arg- Ome, DMQ- MA- Lys (DMQ-MA) -Ile-Arg-Ome, DMQ-MA-Lys (DMQ- MA) -Val- Arg- Ome, DMQ- MA- Lys (DMQ- MA) -Lys (Cbz) -Arg- Ome. The cytotoxic agent conjugated to the N-terminal and the ξ-amino group of Lysine of the tripeptide is 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). The tripeptides were synthesized by coupling protected amino acid residues according to Pfp / DCC methods (Pfp: pentafluorophenol, DCC: N, N’-dicyclohexyl-carbodiimide) in solution. Agarose gel electrophoresis showed that these compounds can cleave supercoiled DNA into open-circular form in low drug as 4-50 μM without H2O2 Further studies on their cytotoxicity for these conjugates are ongoing.