RNA aptamers are synthetic oligonucleotide-based affinity molecules that utilize unique three-dimensional structures for their affinity and specificity to a target such as a protein. They hold the promise of numerous advantages over biologically produced antibodies; however, the binding affinity and specificity of RNA aptamers are often insufficient for successful implementation in diagnostic assays or as therapeutic agents. Strong binding affinity is important to improve the downstream applications. We report here the use of the phosphorodithioate (PS2) substitution on a single nucleotide of RNA aptamers to dramatically improve target binding affinity by ∼1000-fold (from nanomolar to picomolar). An X-ray co-crystal structure of the α-thrombin:PS2-aptamer complex reveals a localized induced-fit rearrangement of the PS2-containing nucleotide which leads to enhanced target interaction. High-level quantum mechanical calculations for model systems that mimic the PS2 moiety and phenylalanine demonstrate that an edge-on interaction between sulfur and the aromatic ring is quite favorable, and also confirm that the sulfur analogs are much more polarizable than the corresponding phosphates. This favorable interaction involving the sulfur atom is likely even more significant in the full aptamer-protein complexes than in the model systems.
The structure of gymnemagenin (3 beta,16 beta,21 beta,22 alpha,23,28-hexahydroxy-olean-12-ene), the sapogenin of the antisweet principles of Gymnema sylvestre, was established by X-ray analysis of the 3 beta,23;21 beta,22 alpha-di-O-isopropylidene derivative. On the basis of this result, the structure of deacylgymnemic acid was elucidated as the 3-O-beta-glucuronide from the carbon-13 nuclear magnetic resonance spectra. Five antisweet principles, gymnemic acid-III, -IV, -V, -VIII, and -IX, were isolated in pure states from the hot water extract of leaves of Gymnema sylvestre. Of these, three (GA-III, -IV, and -V) were known, while two (GA-VIII and -IX) were new compounds. The structures of GA-VIII and -IX were elucidated as 3'-O-beta-D-arabino-2-hexulopyranosyl gymnemic acid-III and -IV, respectively.
A new ent-kaurene beta-D-glucoside was isolated from Rabdosia rubescens, together with the known compounds oridonin, ponicidin, and pedalitin. The structure of new compound was determined, on the basis of spectral data and X-ray crystallographic analysis, to be ent-7 beta,20-epoxy-kaur-16-ene-1 beta,6 alpha,7 alpha,14 alpha,15 alpha-pentanol 1-O-beta-D-glucopyranoside.
For entire roller embedded shapemeter roll, the temperature differences and radial relative displacements of contact node pairs on the interference fit surface between the framework’s top surface and roll body’s inner hole surface, and the sensor pre-pressure were analyzed using the finite element technology in cold reversible rolling passes. The influences of temperature differences on radius relative displacements of the contact node pairs and the sensor pre-pressure were obtained. The results show that the maximum temperature difference of the contact node pair occurs in the third rolling pass, and most of radial relative displacements of contact node pairs exceed the value of interference fit, which makes the sensor pre-pressure be close to zero. So the transfer of pressure that the strip applied on the outer surface of shapemeter roll is seriously affected, and the shape measuring signal is interrupted.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.