Synthesis and DNA Cleavage Studies of 2,6-Dimethoxyhydroquinone-3-Mercaptoacetic Acid Conjugates

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 xi -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 mu M without H2O2 and UV irradiation. Further studies on their cytotoxicity for these conjugates are ongoing.

Synthesis of 2,6-Dimethoxyhydroquinone-3-mercaptoacetyl-peptide-chlorambucil Conjugates

This paper reports a continous study of the use of short chain peptides as carriers of a potential antitumor agents: 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). In an effort to carry out anti-cancer drug design, we synthesized another two new DMQ-MA-peptide-chlorambucil (CRB) derivatives: DMQ-MA-Lys(CRB)-Arg-OMe, DMQ-MA-Lys(DMQ-MA)Lys(CRB)-Arg-OMe. These peptide-chlorambucil conjugates were synthesized by coupling protected amino acids in solution and the next conjugation was achieved by reacting with pentafluorophenyl ester of DMQ-MA in DMF. The CRB in side chain was coupled by deblocking the lysyl-carbobenzyloxy protecting group Z and then reacting with the pentafluorophenyl ester of chlorambucil (CRB). Further study on cytotoxicity, DNA binding, and sequence specificity of DNA alkylation of these two new conjugates are investigating.

Synthesis of Some Novel 2,6- Dimethoxyhydroquinone-3-mercaptoacetyl-peptide Conjugates as Potential Antitumor Agents

This paper reports an ongoing study of the use of short chain peptides as carriers of a potential antitumor agents: 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). Three new peptide-DMQ-MA conjugates: DMQ-MA-arg-arg-ome, DMQ-MA-lys(cbz)-arg-ome, DMQ-MA-lys(cbz)-arg-arg-ome were synthesized by coupling protected amino acids in solution and the next conjugation was achieved by reacting with pentafluorophenyl ester of DMQ-MA in DMF, and further study on their ability to inhibit human pulmonary adenocarcinoma cell line (PC-9 cells) and oral epidermoid carcinoma cell line (KB) are investigating.

Synthesis, and Investigation of the Reactive Oxygen Species of a Novel Cyclicpeptide-2,6-dimethoxyhydroquinone-3- mercaptoacetic Acid Conjugate

In this paper, we report the synthesis of a potential anti-cancer agent: Cyclo[Val-Lys(DMQ-MA)-Gaba]. The cytotoxic agent conjugated to the N-terminal and the xi -amino group of lysine of the tripeptide is 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). By employing the rhodamine B degradation method and ESR spectra, we testify the reactive oxygen species - hydroxyl radicals produced by the drug.