title: Design of artificial transcriptional activators with rigid poly-L-proline linkers.
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 A length range. We find that there is an optimal linker length which separates the DNA and the activation region for transcription activation.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Paramjit S
authors.initials: PS
authors.lastname: Arora
authors.forename: Aseem Z
authors.initials: AZ
authors.lastname: Ansari
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Best
authors.forename: Mark
authors.initials: M
authors.lastname: Ptashne
authors.forename: Peter B
authors.initials: PB
authors.lastname: Dervan
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000138:chemical synthesis / Q000737:chemistry*; D015533:Transcriptional Activation
chemical_list: D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D010455:Peptides; D014157:Transcription Factors; C011083:polyproline