Characterization and solubilization of pyrrole-imidazole polyamide aggregates.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Hargrove, AE; Raskatov, JA; Meier, JL; Montgomery, DC; Dervan, PB

Published Date

  • June 2012

Published In

Volume / Issue

  • 55 / 11

Start / End Page

  • 5425 - 5432

PubMed ID

  • 22607187

Pubmed Central ID

  • PMC3375050

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

International Standard Serial Number (ISSN)

  • 0022-2623

Digital Object Identifier (DOI)

  • 10.1021/jm300380a


  • eng