DNA-polyamine conjugates

A phosphate-modified spermine has also been conjugated to nucleotide sequences, increasing the counter-strand affinity as evidenced by moiutoring the corresponding melting temperatures [62]. Biophysical and in vitro data supported the potentially favorable properties expected for DNA-polyamine conjugates. However, modification of 2 -deoxy-2 -succinylamido-uridine led to substantial decrease in counter-strand affinity when incorporated internally in DNA [62]. 

Hong, K., Zheng, W., Baker, A., Papahadjopoulos, D. (1997). Stabilisation of cationic liposome/DNA complexes by polyamines and polyethylenglycol-phospholipid conjugates for efficient in vivo gene delivery. FEBS Lett., 414, 187-192. 

Dextran-spermine-based conjugates have been prepared via reductive amination between oxidised dextran and spermine [11]. Spermine, a naturally occurring linear polyamine, is involved in cellular metabolism and is a polycation at physiological pH. Dextran was initially oxidised with potassium periodate and the obtained dialdehyde derivative was then reacted under basic conditions with spermine. Dextran-spermine displayed particularly high transfection efficiency, which was attributed to the unique complexation properties between DNA and the grafted spermine moieties. Dextran-spermine and their derivatives have shown high transfection of p-DNA both in vitro and in vivo [12]. 

However, the cleavage of many polyamine-coupled biomolecules require even milder cleavage conditions from the resin, such as DNA conjugates that are hydrolyzed when treated with high concentrations of TEA. 

Schemes DNA conjugation to polyamines on ArgoGe/-NH2, as reported by Kim and Diamond [207]...

Incorporation of an anthraquinone moiety, attached through an acyclic backbone unit, into a duplex DNA such that the anthraquinone was opposed to 5-methyl-dC resulted in an efficient one-electron oxidation to 5-formyl-dC or 5-hydroxymethyl-dC. Treatment of the duplex with hot piperidine led to strand-specific cleavage at the oxidised cytosine base. An anthraquinone has been used to link chimeric a-p oligonucleotides for formation of alternate-stranded triplexes. The two oligonucleotides were linked through a substituted propionic acid derivative which was further conjugated to the anthraquinone via various polyamines. 

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