Syntheses of [12]aneN3-oligopeptide conjugates as effective DNA condensation agents.

With the aim to develop effective and low toxicity DNA condensation agents, a series of oligopeptide derived macrocyclic polyamine [12]aneN(3) conjugates 7a-h·3HCl have been designed and synthesized through multi-step amidation reactions. Structure-property study through gel electrophoresis proved that the conjugates containing high hydrophobic ending amino acids exhibited effective condensation ability at concentration of 150-250 µM, which was further confirmed by dynamic light scattering and atomic force microscopy experiments. EB displacement assay, ionic salt effect, and structure-property relationship in gel electrophoresis indicated that DNA condensation resulted from both the electrostatic interaction of [12]aneN(3) unit and hydrogen-bonding/hydrophobic multi-interaction of oligopeptide moiety in the conjugates with DNA. The reversible condensation process and their low cytotoxicity suggest that the new condensing agents are potential for the development of non-viral vectors.

Synthesis of [12]aneN3-dipeptide conjugates as metal-free DNA nucleases.

In this Letter, a series of macrocyclic polyamine [12]aneN(3)-dipeptide conjugates as a new type of metal-free nucleases were synthesized and fully characterized with (1)H NMR, (13)C NMR, IR, and HR-MS. Results indicate that these conjugates can bind to calf thymus DNA mainly through electrostatic interaction and can cleave the plasmid DNA at 200 µM (pH 7.2, 37°C), with an acceleration of 10(6)-fold via hydrolytic pathway.

Effective and reversible DNA condensation induced by bifunctional molecules containing macrocyclic polyamines and naphthyl moieties.

A series of bifunctional molecules containing macrocyclic polyamines [12]aneN(3) and naphthyl moieties 1-3(a, b) have been designed and synthesized through efficient N-alkylation and copper-mediated alkyne-azide click reactions. Experiments on gel electrophoresis, dynamic light scattering and atomic force microscopy confirmed that 2b and 3b with two [12]aneN(3) units efficiently induced the DNA condensation at the concentration of 120 µM in less than 5 min. The condensation mechanism was studied by EB displacement fluorescence spectra, viscosity titration, and ionic strength effects. The condensation process was found to be reversible, and the presence of both naphthyl and [12]aneN(3) units in the molecules was proved to be necessary for the effective DNA condensation inductions. Cytotoxicity assay showed that the presence of triazole moieties can result in lower toxicity.

Synthesis of mono- and di-[12]aneN3 ligands and study on the catalytic cleavage of RNA model 2-hydroxypropyl-p-nitrophenyl phosphate with their metal complexes.

A series of mono- and di-[12]aneN(3) ligands 1-6, which contain different substituents on the coordinating backbone, different linkers between two [12]aneN(3) units and different N-methylation on the [12]aneN(3) units, have been synthesized and fully characterized. The catalytic activities of their metal complexes on the cleavage of RNA model phosphate 2-hydroxypropyl-p-nitrophenyl phosphate (HPNPP) varied with the structures of the ligands and metal ions. Click reactions afforded an efficient method to prepare a series of [12]aneN(3) ligands, however, the incorporation of triazole moieties reduced the catalytic activities due to their coordination with metal ions and the strong inhibition from the triflate counter ion. Dinuclear zinc(II) complexes containing an m-xylyl bridge showed higher catalytic activities with synergistic effects up to 700-fold. Copper(II) complexes with the ligands without triazole moieties proved to be highly reactive and showed strong cooperativity between the two copper(II) ions. In terms of k(2), dinuclear complexes Zn(2)-3b, Zn(2)-3d, Zn(2)-4b, and Cu(2)-4b afforded activities of 7.9 × 10(5), 3.9 × 10(4), 9.0 × 10(4), and 8.1 × 10(4)-fold higher than that of methoxide. The ortho arrangement of the two [12]aneN(3) units and the presence of 5- or 2-positioned substituents in the benzene ring as well as N-methylation of [12]aneN(3) units greatly reduced the catalytic activities due to the steric effects. These results clearly indicate that the structures of the linker between two [12]aneN(3) units play very important role in their catalytic synergistic effects.