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Selectivity of spermine homologs on triplex DNA stabilization

Antisense and Nucleic Acid Drug Development, ISSN: 1087-2906, Vol: 9, Issue: 2, Page: 221-231
1999
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Article Description

We synthesized seven homologs of spermine (HN(CH)NH(CH)(n)NH(CH)NH, where n = 2-9; n = 4 for spermine) and studied their effects on melting temperature (T(m)), conformation, and precipitation of poly(dA).2poly(dT). The triplex DNA melting temperature, T(m1) was 34.4°C in the presence of 150 mM KCl. Addition of spermine homologs increased T(m1) in a concentration-dependent and structure-dependent manner, with 3-6-3 (n = 6) exerting optimal stabilization. The dT(m1)/dlog[polyamine] values were 9-24 for these compounds. The duplex melting temperature, T(m2) was insensitive to homolog concentration and structure, suggesting their ability to stabilize triplex DNA without altering the stability of the underlying duplex. Circular dichroism spectral studies revealed Ψ-DNA formation in a concentration-dependent and structure-dependent manner. Phase diagrams were constructed showing the critical ionic/polyamine concentrations stabilizing different structures. These compounds also exerted structural specificity effects on precipitating triplex DNA. These data provide new insights into the ionic/structural determinants affecting triplex DNA stability and indicate that 3-6-3 is an excellent ligand to stabilize poly(dA).2poly(dT) triplex DNA under physiologic ionic conditions for antigene therapeutics.

Bibliographic Details

Thomas Antony; Thresia Thomas; Leonard H. Sigal; T. J. Thomas; Akira Shirahata

Mary Ann Liebert Inc

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics

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