Cytotoxic Peptides: Naphthoquinonyl Derivatives of Luteinizing Hormone-Releasing Hormone

In an attempt to produce efficient cytotoxic derivatives of luteinizing hormone-releasing hormone (LH-RH), two novel 1,4-naphthoquinone derivatives of [D-Lys⁶]-LH-RH were synthesized primarily by solid-phase peptide synthesis, in good yield and high purity. The ability of each analog to produce reactive oxygen species using enzymatic reduction, i.e. NADPH-cytochrome P-450 reductase, was evaluated employing electron spin resonance (ESR) spectroscopy and spin-trapping techniques. The ESR results suggest that the novel cytotoxic analogs are extremely effective in generating oxygen radicals.     

Cytotoxic Peptides: Naphthoquinonyl Derivatives of Luteinizing Hormone-Releasing Hormone

Summary In an attempt to produce efficient cytotoxic derivatives of luteinizing hormone-releasing hormone (LH-RH), two novel 1,4-naphthoquinone derivatives of [d-Lys⁶]-LH-RH were synthesized primarily by solid-phase peptide synthesis, in good yield and high purity. The ability of each analog to produce reactive oxygen species using enzymatic reduction, i.e. NADPH-cytochrome P-450 reductase, was evaluated employing electron spin resonance (ESR) spectroscopy and spin-trapping techniques. The ESR results suggest that the novel cytotoxic analogs are extremely effective in generating oxygen radicals.     

Novel naphthoquinonyl derivatives: Potential structural components for the synthesis of cytotoxic peptides

Summary Syntheses and physicochemical properties are described of several novel naphthoquinonyl amino acid derivatives, which are potential components in cytotoxic peptide conjugates. These compounds include N - and N -naphthoquinonyl derivatives of lysine as well as N-naphthoquinonyl-carboxylic derivatives. The former class of compounds can be employed as building blocks in a stepwise peptide synthesis, whereas the latter two are adequate for postpeptide chain-assembly modifications. The ability of the naphthoquinonyl derivatives to produce semiquinone radicals and hydroxyl radicals (OH), using chemical (i.e. NaBH₄) and enzymatic (i.e. NADPH-cytochrome P-450 reductase) routes, respectively, was evaluated employing electron spin resonance spectroscopy.