Simultaneous quantitative determination of 5 - aza - 2 ′ - deoxycytidine genomic incorporation and DNA demethylation by liquid chromatography tandem mass spectrometry as exposure - response measures
of nucleoside analog DNA methyltransferase inhibitors.
Kariko, K., Buckstein, M., Ni, H. & Weissman, D. Suppression of RNA recognition by Toll - like receptors: the impact
of nucleoside modification and the evolutionary origin of RNA.
Previous efforts made the parts
of a nucleoside separately and then linked them together — a stepwise process that generally yields a useless mess of many possible configurations.
Resistance is a significant problem with the ongoing use
of nucleoside analogs, which when applied topically to the eye can cause serious side effects including glaucoma.
But findings in Moore's lab supported the view that mRNA strands with more
of the nucleosides that tend to form tight bonds are, in fact, easier for ribosomes to translate.
This cellular machinery translates its sequence of four kinds
of nucleosides — adenosine, cytidine, uridine, and guanosine — into a protein.
However, very early I discovered that this was not the case and later on I found out that cells are not ready to recycle these modified forms
of nucleosides.
The presence
of nucleosides is «highly regulated» within the mitochondria, Cohen explained.
Not exact matches
«We saw clearance
of the virus at concentrations
of BX795 that were five times lower than concentrations
of antiviral compounds in available
nucleoside analogs,» Shukla said.
By doing so, they have successfully captured the snapshot
of the intermediate state where the viral helicase exactly binds to the
nucleoside triphosphate ATP and a metal ion, two essential molecules required for the helicase to do its job.
The scientists suggest that flavivirus helicases could have evolved a conserved motor to convert chemical energy from
nucleoside triphosphate to mechanical energy to unwind their genetic material, but the motors
of the flaviviruses move in distinct ways to access their genomic RNA.
All but one fall into one
of three categories — either
nucleoside or nonnucleoside reverse transcriptase inhibitors or protease inhibitors — based on the part
of the virus they target.
Assembling mRNA using pseudouridine, a
nucleoside variant that occurs naturally in the body, greatly reduced the tendency
of immune sentinels called dendritic cells to shoot out inflammatory molecules in response, they reported in 2005.
«It would be stupendous to see the data out
of Moderna,» says Paul Agris, an analytical biochemist at the State University
of New York in Albany's RNA Institute who has spent decades studying the consequences
of modifying RNA
nucleosides.
The team knew that the frequency and placement
of the modified
nucleosides in the strand changed how it folded, and hence how it interacted with the ribosome.
And because trillions upon trillions
of different
nucleoside sequences can code for the same protein, there were plenty
of ways to engineer more efficient ones — providing they could be predicted.
It hasn't revealed which modified
nucleoside is in its newest generation
of drug candidates.
Initially operating in «stealth mode» — without announcement
of its existence — Moderna's team screened mRNA assembled from various modified
nucleosides and hit on one called 1 - methylpseudouridine.
Even between mRNAs with the same sequence, they were finding that different modified
nucleosides produced different amounts
of protein.
The same is true for a powerful
nucleoside analog — a small molecule that's cheap to make — developed by the U.S. Army Medical Research Institute
of Infectious Diseases.
Molecular basis for the immunostimulatory activity
of guanine
nucleoside analogs: activation
of Toll - like receptor 7.
The tested compound looks and acts like the chemical building blocks
of DNA, called
nucleosides.
Selectivity
of the therapeutic approach is achieved by producing an enzyme called E. coli purine
nucleoside phosphorylase (PNP) directly within tumor cells and using the enzyme to generate novel chemotherapy in the tumor mass itself.
While the hospital advocates transitioning Charlie to end -
of - life palliative care — officials have stated that «he has no quality
of life and no real prospect
of any quality
of life» — his parents want him to undergo a highly experimental treatment in the United States called
nucleoside bypass therapy.
Nucleoside bypass therapy, which was developed by Dr. Michio Hirano
of Columbia University Medical Center, involves an oral dose
of extra
nucleosides that rebalances the concentration
of these essential building blocks inside the mitochondria.
Strain Promoted Click Chemistry
of 2 - or 8 - Azidopurine and 5 - Azidopyrimidine
Nucleosides and 8 - Azidoadenosine Triphosphate with Cyclooctynes.
It does this, Ebright said, by mimicking a
nucleoside - triphosphate, one
of the «building blocks»
of RNA that is essential for life.
We present simple cascade reactions that lead to the formation
of methylated and aminoacylated
nucleosides under prebiotic conditions.
Current anti-HBV therapeutics are interferon and
nucleoside analog inhibitors
of HBV reverse transcriptase (Pol).
Mass - spectrometry - based methods have been at the forefront
of identifying and quantifying modified
nucleosides.
However, they often require synthetic reference standards, which do not exist in the case
of many modified
nucleosides, and this therefore impedes their analysis.
Sequencing - by - synthesis is carried out on all these clusters simultaneously, using fluorescent reversible terminators, which allow one and only one
nucleoside to be added to a growing strand in a single cycle
of sequencing.