Structurally Diverse Polyamines: Solid‐Phase Synthesis and Interaction with DNA

Abstract

A versatile solid-phase approach based on peptide chemistry was used to construct four classes of structurally diverse polyamines with modified backbones: linear, partially constrained, branched, and cyclic. Their effects on DNA duplex stability and structure were examined. The polyamines showed distinct activities, thus highlighting the importance of polyamine backbone structure. Interestingly, the rank order of polyamine ability for DNA compaction was different to that for their effects on circular dichroism and melting temperature, thus indicating that these polyamines have distinct effects on secondary and higher-order structures of DNA.

Highly Concentrated Ethanol Solutions: Good Solvents for DNA as Revealed by Single‐Molecule Observation

“…The cyanine dye YOYO-1 at ac oncentration of 0.2 mm was added to the DNA solution, together with the antioxidant 2-ME [4 %( v/v)],t ov isualize individual DNA molecules by fluorescence microscopy.D etails of the experimental conditions for the observation of single DNA molecules was essentially the same as in our previous study. [10] Observations were carried out at around 24 8C with aD NA concentration of 30 mm in nucleotide units. Fluorescence images of DNA molecules were observed using amicroscope (Axiovert 135 TV,C arl Zeiss, Germany) equipped with an oil-immersed 100 o bjective lens, and recorded on DVDs by using ah ighly sensitive electron-bombarded charge-coupled device (EBCCD) (Hamamatsu Photonics, Hamamatsu, Japan).…”

“…The cyanine dye YOYO‐1 at a concentration of 0.2 μ m was added to the DNA solution, together with the antioxidant 2‐ME [4 % (v/v)], to visualize individual DNA molecules by fluorescence microscopy. Details of the experimental conditions for the observation of single DNA molecules was essentially the same as in our previous study . Observations were carried out at around 24 °C with a DNA concentration of 30 μ m in nucleotide units.…”

Inhibition of FAD-dependent lysine-specific demethylases by chiral polyamine analogues

“…Polyamines 1-4 were synthesized by the solid-phase method, as reported previously. 26,27 In brief, once the peptide was constructed on solid support using standard Fmoc method, the resin was treated with BH 3 -THF to reduce the backbone amide functionality. The resultant polyamine was then treated with piperidine while still attached to the solid support, followed by TFA cleavage.…”

“…These polyamines all contain a (4-methoxyphenyl) propyl group, which shows strong UV absorbance and is helpful for purication by reversed-phase HPLC (RP-HPLC). 26,27 We chose (4-methoxyphenyl)propyl group, since it is readily available, relatively small, and stable under the condition of amide reduction. Also, we envisioned that this structure might participate in the favorable hydrophobic interaction with LSDs, since phenyl group is frequently appeared in the small molecule LSD1 inhibitors.…”

“…19 The solid-phase method is relatively simple and possible to synthesize various types of polyamines. 27 Polyamines 5-7 were prepared according to the literature. 28,29 Polyamines 1-6 contain ve primary, secondary, tertiary, quaternary amino or ammonium groups, whereas 7 has only four amino groups.…”