Year: 2012
Type: article
Abstract: 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.
Source: Journal of Medicinal Chemistry
DOI: 10.1021/jm300380a
Institution: California Institute of Technology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: G1605681794, PREDOCTORAL TRAINING IN BIOLOGY AND CHEMISTRY, SEQUENCE SPECIFIC RECOGNITION OF DNA, G3629900643, Regulation of Gene Expression by DNA Binding Ligands, Programmable DNA Binding Oligomers for Control of Transcription, DNA-binding polyamides as Hedgehog inhibitors in human carcinoma
OpenAlex ID: W2072522264