1. Methionine sustituted polyamides are RNAse mimics that inhibit translation.
- Author
-
Kumar R, Garneau P, Nguyen N, William Lown J, and Pelletier J
- Subjects
- Animals, Asparagine chemistry, In Vitro Techniques, Luciferases, Firefly antagonists & inhibitors, Luciferases, Firefly biosynthesis, Luciferases, Firefly genetics, Lysine chemistry, Molecular Mimicry, Nylons chemistry, Nylons pharmacology, Protein Biosynthesis drug effects, Protein Synthesis Inhibitors chemistry, Protein Synthesis Inhibitors pharmacology, RNA chemistry, RNA metabolism, Rabbits, Reticulocytes metabolism, Structure-Activity Relationship, Tryptophan chemistry, Aminoglycosides chemistry, Imidazoles chemistry, Methionine chemistry, Nylons chemical synthesis, Protein Synthesis Inhibitors chemical synthesis, Ribonucleases chemistry
- Abstract
RNAse mimics are small molecules that can cleave RNA in a fashion similar to ribonucleases. These compounds would be very useful as gene specific reagents if their activities could be regulated and targeted. We demonstrate here that polyamides with methionine substituents show enhanced RNA cleavage activity relative to other polyamides. Conjugation of these compounds to aminoglycosides produced RNAse mimics that are capable of inhibiting eukaryotic protein synthesis. As a new class of compounds capable of interacting with nucleic acids, these novel aminoglycoside-polyamides constitute promising scaffolds for the construction of nuclease mimics with biological activity.
- Published
- 2004
- Full Text
- View/download PDF