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The new lactam, bearing a C 5)C 6) double bond, was anticipated to afford higher diastereofacial selection resulting from the removal of additional steric hindrance to reagent approach distal to the geminal dimethyl bridge by comparison with the previously studied saturated analogue (the favored mode approach in the saturated analogue).
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A potentially powerful strategy to overcome this apparent affinity barrier is to combine this additivity algorithm with recently described multivalent peptide affinity reagent approaches [31], [43].
Existing affinity reagent development approaches, including protein mutagenesis, directed evolution, and fragment-based design utilize large libraries and/or require structural information thereby adding time and expense.
This algorithm does not require large libraries or structural information, which are important characteristics that enable rapid, low-cost generation of high-affinity peptide ligands and differentiate this algorithm from other affinity reagent development approaches.
Cells pretreated with GA, generated higher levels of ROS in the whole dose range from 0.5 to 4 Gy which, however, were shown to attenuate faster as compared to the decay kinetics of ROS measured in the cells which were not pre-treated with the reagent and approaching equal levels at later time points post-irradiation.
We recently proposed a transdermal blood- and reagent-free approach based on hemozoin-generated vapor nanobubbles (H-VNBs) (22 ) in which malaria parasite specific endogenous nanocrystals of hemozoin are optically excited in vivo with a safe and short laser pulse (delivered to blood vessels through the skin).
With this approach, reagent is delivered only after 'priming' pressure pulses: we show in two examples that unintended reagent delivery (leakage) prior to the priming pulses is non-detectable.
Given the anionic nature of the species proposed to attack the prochiral carbonyl compound in the generally accepted mechanism for trifluoromethylation using the Ruppert Prakash reagent, an early approach to induce asymmetry aimed to take advantage of a chiral cation strategy.
While FcγRIs could be attached to a lipid coated nanoparticle by synthesizing a fusion protein with a transmembrane domain that inserts into the lipid layer, all lipids and reagents in our approach are commercially available thereby avoiding the need for specialized synthesis methods.
Thus, although these data do not prove that the freezing procedure is indeed a requirement for stable storage over longer periods of time for all commercial reagents, they support the feasibility of this approach for reagents of all sources tested.
Employing reagent based skeletal diversity approach; a facile synthesis of bis heterocycles with different heterocyclic rings at C-3 position of the quinoline moiety has been accomplished.
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