Locked nucleic acid: modality, diversity, and drug discovery.

Over the past 20 years, the field of RNA-targeted therapeutics has advanced based on discoveries of modified oligonucleotide chemistries, and an ever-increasing understanding of how to apply cellular assays to identify oligonucleotides with improved pharmacological properties in vivo. Locked nucleic acid (LNA), which exhibits high binding affinity and potency, is widely used for this purpose. Our understanding of RNA biology has also expanded tremendously, resulting in new approaches to engage RNA as a therapeutic target. Recent observations indicate that each oligonucleotide is a unique entity, and small structural differences between oligonucleotides can often lead to substantial differences in their pharmacological properties. Here, we outline new principles for drug discovery exploiting oligonucleotide diversity to identify rare molecules with unique pharmacological properties.

Efficient colorimetric and fluorescent detection of fluoride in DMSO-water mixtures with arylaldoximes.

Fluoride detection through hydrogen bonding or deprotonation is most commonly achieved using amide, urea or pyrrole derivatives. The sensor molecules are often complex constructs and several synthetic steps are required for their preparation. Here we report the discovery that simple arylaldoximes have remarkable properties as fluoride anion sensors, providing distinct colorimetric or fluorescent readouts, depending on the structure of the arylaldoxime. The oximes showed exceptional selectivity towards fluoride over other typical anions, and low detection limits for fluoride in both DMSO and DMSO-water mixtures were obtained.