Ion-Pair-Enhanced Double-Click Driven Cell Adhesion and Altered Expression of Related Genes

Kitagawa, Kakuya; Okuma, Nao; Yoshinaga, Moeka; Takemae, Hitoshi; Sato, Shoma; Nakabayashi, Seiichiro; Yoshikawa, Hiroshi; Suganuma, Masami; Luedtke, Nathan W.; Matsuzaki, Takahisa; Tera, Masayuki

doi:10.1021/acs.bioconjchem.2c00569

Cited by 2 publications

(1 citation statement)

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“…Although isolation of monocycloaddition intermediates has proven elusive in vitro, stepwise cycloaddition reactions have been demonstrated for bioorthogonal applications, where the low effective concentration of the initial dipole is sufficiently small to avoid further secondary cycloaddition. 25 The spatial distribution of the nitrones on the bacterial cell surface must be sufficient to enable the slower reacting azide to perform the second cycloaddition, as our observations indicate.…”

Section: ■ Results and Discussionmentioning

confidence: 74%

Mechanistic Analysis of Bioorthogonal Double Strain-Promoted Alkyne–Nitrone Cycloadditions Involving Dibenzocyclooctadiyne

Bilodeau,

Margison,

Masoud

et al. 2023

ACS Chem. Biol.

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The reactions of nitrones with cyclooctadiynes were studied to establish the relative rates of sequential reactions and to determine the limits and scope of this bioorthogonal chemistry. We have established the second-order rate constants for the consecutive additions of a variety of nitrones onto diyne and studied the structure−activity relationships via Hammett plots. Results show that the addition of the second nitrone to the monointermediate occurs significantly faster than the first, with both reactions being faster than analogous reactions with azides. Computational chemistry supports these observations. The rate of second addition increases with electron-deficient nitrones, as demonstrated by a large rho value of 2.08, suggesting that the reaction rate can be controlled by nitrone selectivity. To further investigate the kinetic parameters of the reaction, dinitrone monomers containing cyclic and diaryl-nitrones were designed for use in oligomerization applications. Oligomerization was used as a probe to test the limits of the reactivity and attempt to isolate monocycloaddition products. The oligomer formed from a cyclic nitrone reacts faster, and detailed MALDI mass spectrometry analysis shows that monoaddition products exist only transiently and are not isolatable. These studies inform on the scope and limits of this chemistry in a variety of applications. We successfully demonstrated bacterial cell wall labeling using heterogeneous dual cycloadditions involving nitrone and azide dipoles, where the nitrone was the faster reacting partner on the bacterial cell surface.

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Section: ■ Results and Discussionmentioning

confidence: 74%