RNA binding and thiolytic stability of a quinoline-containing helix-threading peptide.
Helix-threading peptides (HTPs) bind selectively to sites predisposed to intercalation in folded RNA molecules placing peptide functional groups into the dissimilar grooves of the duplex. Here we report the design and synthesis of new HTPs with quinoline as the intercalation domain. A quinoline-containing HTP is shown to bind selectively to duplex RNA binding sites. Furthermore, the affinity cleavage pattern generated using an EDTA.Fe modified derivative is consistent with minor groove localization of its N-terminus. This compound binds base-pair steps flanked by single nucleotide bulges on the 3' side on both strands, whereas bulges on the 5' side of the intercalation site do not support binding. Furthermore, unlike acridine HTPs, the quinoline compound is resistant to thiolytic degradation that leads to loss of RNA-binding activity. The RNA-binding selectivity and stability observed for quinoline-containing HTPs make them excellent candidates for further development as regulators of intracellular RNA function.
Krishnamurthy
Malathy
M
Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, USA.
Gooch
Barry D
BD
Beal
Peter A
PA
D001483:Base Sequence; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011804:Quinolines / Q000737:chemistry*; D012313:RNA / Q000737:chemistry* / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D010455:Peptides; D011804:Quinolines; D013438:Sulfhydryl Compounds; D012313:RNA; C037219:quinoline; D012260:Ribonucleases