Design of artificial transcriptional activators with rigid poly-L-proline linkers.
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.
Arora
Paramjit S
PS
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Ansari
Aseem Z
AZ
Best
Timothy P
TP
Ptashne
Mark
M
Dervan
Peter B
PB
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
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D010455:Peptides; D014157:Transcription Factors; C011083:polyproline