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Characterization and Solubilization of Pyrrole–Imidazole Polyamide Aggregates
Ist Teil von
Journal of medicinal chemistry, 2012-06, Vol.55 (11), p.5425-5432
Ort / Verlag
United States: American Chemical Society
Erscheinungsjahr
2012
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
To optimize the biological activity of pyrrole–imidazole polyamide DNA-binding molecules, we characterized the aggregation propensity of these compounds through dynamic light scattering and fractional solubility analysis. Nearly all studied polyamides were found to form measurable particles 50–500 nm in size under biologically relevant conditions, while HPLC-based analyses revealed solubility trends in both core sequences and peripheral substituents that did not correlate with overall ionic charge. The solubility of both hairpin and cyclic polyamides was increased upon addition of carbohydrate solubilizing agents, in particular, 2-hydroxypropyl-β-cyclodextrin (HpβCD). In mice, the use of HpβCD allowed for improved injection conditions and subsequent investigations of the availability of polyamides in mouse plasma to human cells. The results of these studies will influence the further design of Py-Im polyamides and facilitate their study in animal models.