ABSTRACT
Metabolic incorporation of unnatural functionality on glycans has allowed chemical biologists to observe and affect cellular processes. Recent work has resulted in glycan-fluorophore structures that allow for direct visualization of glycan-mediated processes, shining light on their role in living systems. This work describes the serendipitous discovery of a small chemical reporter-fluorophore. Investigations into the mechanism of fluorescence arising from (trimethylsilyl)methylglycine appended on mannosamine suggest rigidity and restriction of lone pair geometry contribute to the fluorescent behaviour. In fact, in situ cyclization and encapsulation in cucurbit[7]uril enhance fluorescence to levels that can be observed in live cells. While the reported unnatural mannosamine does not traverse the sialic acid biosynthetic pathway, this discovery may lead to small, "turn-on" chemical reporters for incorporation in living systems.
ABSTRACT
High-affinity guests have been reported for the macrocyclic host cucurbit[7]uril (CB[7]), enabling widespread applications, but hindering CB[7] materials from being returned to their guest-free state for reuse. Here, we present polyhedral boron clusters (carboranes) as strongly binding, yet easily removable, guests for CB[7]. Aided by a Pd-catalyzed coupling of an azide anion, we prepared boron-functionalized 9-amino-ortho-carborane that binds to CB[7] with a Ka ≈ 1010 M-1. Upon basic treatment, ortho-carborane readily undergoes deboronation to yield anionic nido-carborane, a poor guest for CB[7], facilitating recovery of guest-free CB[7]. We showcase the utility of the modified ortho-carborane guest by recycling a CB[7]-functionalized resin. With this report, we introduce stimuli-responsive decomplexation as an additional consideration in the design of high-affinity host-guest complexes.
Subject(s)
Boron Compounds/chemistry , Bridged-Ring Compounds/chemistry , Imidazoles/chemistry , Azides/chemistry , Catalysis , Kinetics , Palladium/chemistryABSTRACT
The widespread adoption of the bioorthogonal chemical reporter strategy revolutionized chemical biology. However, its translation to living mammals has been challenging, due to the size/stability properties of the chemical reporter group and/or the reaction kinetics of the labeling step. While developing new bioorthogonal reactions has been the traditional approach to optimizing the bioorthogonal chemical reporter strategy, here we present a different avenue, leveraging intermolecular interactions, to create bioorthogonal host-guest pairs. This approach, deemed "bioorthogonal complexation, does not rely on activated functional groups or second-order rate constants. We utilize the cucurbit[7]uril (CB[7]) scaffold to showcase bioorthogonal complexation and determine that medium-affinity (Ka ≈ 108-109 M-1) guests efficiently label cell surfaces and outperform the strain-promoted azide-alkyne cycloaddition. Finally, we implement bioorthogonal complexation in the chemical reporter strategy through the metabolic incorporation of ortho-carborane into cell-surface glycans and detection with a CB[7]-fluorescein conjugate.