Cyclopropyl and cyclobutyl substituents were well tolerated in this position, but were less potent as the highly active 3S-methyl compound.
By characterizing nucleotide binding, EF-Ts interaction, aminoacyl-tRNA binding, and delivery to the ribosome, we demonstrate that only alanine (or cysteine) can be tolerated in this position and that the serine and methionine substitutions significantly impair aminoacyl-tRNA, but not nucleotide binding.
Khan suspects that she's tolerated in this position in part because she may have money, in part because her notoriety could make her an asset to al Shabaab, and in part because her son, now a tween, may be a potential future asset undergoing grooming to become a well-trained and famous future jihadi.
Substitution on the arene undergoing ruthenation was well tolerated in the position para to the ketone, with OMe- and Cl-containing substrates reacting smoothly with a variety of acrylates (6 f– 6 i).
Electron-rich substrates performed well, with a variety of electron-donating substituents being tolerated in all positions of the aromatic ring (3 a– f).
This indicates that inosine base pairs, although tolerated in some positions, may not necessarily be useful in overcoming mismatches between guide strand and target, although our analysis may not be generalizable given that the binding of dI to each base varies and is context-dependent.
Our structural analyses also rationalise why glycine is poorly tolerated in the P1 position of a substrate and the corresponding peptidyl-CMK.
The variety of substituents tolerated in the meta-position is rather broad and encompasses alkyl and alkoxy groups as well as halogens (entries 2 6).
A range of para- and meta-substituted aryl groups are well tolerated in the α-position of the cyclohexanone, as well as heteroatom-substituted cyclohexanones (198l, m).
Incorporation of multiple halogens into the phenyl ring (Table 3) demonstrated that fluoride is tolerated in the 2-position of the phenyl ring (30– 32), and the 2-CF3 pyridine analogue (31) showed improvement over the HTS lead (3).
