3D‐QSAR uses statistical techniques to correlate calculated structural properties with target properties like biological activity. The comparison of calculated structural properties is dependent upon the relative orientations of molecules in a given data set. Typically molecules are aligned by performing an overlap of common structural units. This “alignment rule” is adequate for a data set, that is closely related structurally, but is far more difficult to apply to either a diverse data set or on the basis of some structural property other than shape, even for sterically similar molecules. In this work we describe a new algorithm for molecular alignment based upon optimization of molecular similarity indices. We show that this Monte Carlo based algorithm is more effective and robust than other optimizers applied previously to the similarity based alignment problem. We show that QSARs derived using the alignments generated by our algorithm are superior to QSARs derived using the more common alignment of fitting of common structural units. © 1997 by John Wiley & Sons, Inc. J Comput Chem 18: 1344–1353, 1997

The full understanding of dynamics of cellular processes hinges on the development of efficient and non-invasive labels for intracellular RNA species. Light-up aptamers binding fluorogenic ligands show promise as specific labels for RNA species containing those aptamers. Herein, we took advantage of existing, non-light-up aptamers against small molecules and demonstrated a new class of light-up probes in vitro. We synthesized two conjugates of thiazole orange dye to small molecules (GMP and AMP) and characterized in vitro their interactions with corresponding RNA aptamers. The conjugates preserved specific binding to aptamers while showing several 100-fold increase in fluorescence of the dye (the ‘light-up’ property). In the presence of free small molecules, conjugates can be displaced from aptamers serving also as fluorescent sensors. Our in vitro results provide the proof-of-concept that the small-molecule conjugates with light-up properties can serve as a general approach to label RNA sequences containing aptamers.

No abstract

No abstract

No abstract