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Cleavage of C-O bond at the D-ring and reorganization of the D-ring renders the tasteless limonoate A-ring lactone that can be alternatively glycosylated (as occurs during normal maturation) or converted into bitter limonin [ 17].
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The simulation revealed hPR Cys891 as the sole but weak hydrogen bonding partner of progesterone in the D-ring.
Hydroxylation at the 16α position of the D-ring produces 16-pathway metabolites [ 8].
While unexpected, this behavior of E4 may be a consequence of an efficient intramolecular network of hydrogen bonds, operating among the three OH groups in the D-ring that in some way effectively suppresses their polar nature, thus allowing the D-ring to reside more comfortably in the hydrophobic core of the bilayer.
The carbonyl oxygen atom (close to E ring) of the D-ring was stabilized by a hydrogen bonding interaction with the side chain amide group of Gln725 (-CO H2NOC-Gln725).
The hydroxyl group of the D-ring (17 β-OH) forms a single hydrogen bond with His524 (His524
Newly discovered SL mimics only have the D-ring with an appropriate leaving group at C-5.
We defined these ring extensions on the B-ring as the D-ring.
One of them, scaffold 6 (Figure 1C), can be designed with the intention of providing an additional phenolic group at the D ring to add the third hydrogen bond with the carbonyl group of Glu81.
Two more hydrogen bonds are formed by the D ring with a backbone amide of the P-loop and the side chain of Glu239 (Table 1).
This orientation is rather counterintuitive, although an efficient intramolecular network of hydrogen bonds among the three D-ring OH groups might be masking their polarity more effectively than the lone 17β-OH in E2.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com