Design of Artificial Transcriptional Activators with Rigid Poly-l-proline Linkers

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Abstract
Typical eukaryotic transcriptional activators are composed of distinct functional domains, including a DNA binding domain and an activating domain. Artificial transcription factors have been designed wherein the DNA binding domain is a minor groove DNA binding hairpin polyamide linked by a flexible tether to short activating peptides, typically 16−20 residues in size. In this study, the linker between the polyamide and the peptide was altered in an incremental fashion using rigid oligoproline “molecular rulers” in the 18−45 Å length range. We find that there is an optimal linker length which separates the DNA and the activation region for transcription activation.