Methionine-substituted polyamides conjugated to aminoglycosides act as RNAse mimics capable of inhibiting eukaryotic protein synthesis, providing a novel scaffold for nuclease mimics.
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May enable RNA-targeted therapeutics; leaves open translation to disease models and clinical use.
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.
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Kumar et al. (2004) studied this question.
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