Indoxyl-glucosides bearing tethers for enzymatically triggered cross-linking

Sato, Daisuke; Wu, Zhiyuan; Dou, Jinghuai; Son, Juno; Lindsey, Jonathan S.

doi:10.1039/d2nj06267d

Cited by 3 publications

(6 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We prepared indoxyl-glucosides that bear an alkoxy tether at the indoxyl 5-position [5,6] the propargyloxy substituent, the yield was <5% (III), but increased upon inclusion of flanking bromine atoms, affording 56% with one bromine (IV) or an essentially quantitative yield with two bromines (V). Nearly identical results were obtained with the methoxycarbonyl substituent [5], and similar results have been observed with various derivatized PEG groups [9].…”

Section: Introductionsupporting

confidence: 83%

“…We previously prepared 25 indoxyl-glucosides [ 5 , 6 , 9 ], and here we considered whether indoxyl β-glucosides could be converted directly to the corresponding indoxyl β-glucuronides. The primary hydroxy group (6-position) of a methyl α-glucoside or phenyl β-glucoside was reported to undergo selective oxidation to give the corresponding glucuronide upon treatment with 2,2,6,6-tetramethyl-1-piperidinyloxy free radical (TEMPO) and a co-oxidant such as PhI(OAc) 2 or t -BuOCl [ 18 , 19 ].…”

Section: Resultsmentioning

confidence: 99%

“…The ability to cross-link molecules under physiological conditions may underpin a range of applications in bioorganic chemistry [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. One class of molecules that has served well in this regard contains the indoxyl motif, the spontaneous oxidative dimerization of which affords the indigoid dye.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tethered Indoxyl-Glucuronides for Enzymatically Triggered Cross-Linking

Son

Dou

et al. 2023

Molecules

Self Cite

View full text Add to dashboard Cite

Indoxyl-glucuronides, upon treatment with β-glucuronidase under physiological conditions, are well known to afford the corresponding indigoid dye via oxidative dimerization. Here, seven indoxyl-glucuronide target compounds have been prepared along with 22 intermediates. Of the target compounds, four contain a conjugatable handle (azido-PEG, hydroxy-PEG, or BCN) attached to the indoxyl moiety, while three are isomers that include a PEG-ethynyl group at the 5-, 6-, or 7-position. All seven target compounds have been examined in indigoid-forming reactions upon treatment with β-glucuronidase from two different sources and rat liver tritosomes. Taken together, the results suggest the utility of tethered indoxyl-glucuronides for use in bioconjugation chemistry with a chromogenic readout under physiological conditions.

show abstract

Section: Introductionsupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tethered Indoxyl-Glucuronides for Enzymatically Triggered Cross-Linking

Son

Dou

et al. 2023

Molecules

Self Cite

View full text Add to dashboard Cite

show abstract

“…8 One approach relies on enzymatically triggered indigogenic cross-linking. [9][10][11][12][13] The indigogenic cross-linking can be triggered by enzyme cleavage in aqueous solution under physiological conditions to afford a chromogenic readout. The cross-linking is covalent, hence the reaction processes are essentially irreversible.…”

Section: Investigation Of Amylose Matricesmentioning

confidence: 99%

Investigation of amylose and tailored amylose matrices for scavenging iodide

Dou,

Sato,

Son

et al. 2023

Molecular and Nanophotonic Machines VI

Self Cite

View full text Add to dashboard Cite

It has been known for two centuries that starch turns blue upon exposure to iodine as well as the combination of iodine and iodide. Starch contains branched-chain polysaccharides (amylopectin) and linear polysaccharides (amylose), the latter a polymer of a-D-glucose units joined by a(1à4) linkages. Amylose forms a linear helix with 6 a-D-glucose units per turn (i.e., one "amylose ring") and one iodide atom bound maximally per turn. Despite extensive work, suitable quantitative data of iodide-amylose binding seemed surprisingly scarce. To fill an apparent lacuna, examination of the intrinsic binding affinity of amylose for iodide (with measurement of "blue values" by absorption spectroscopy) via a factorial design (grid) study showed that >70% occupancy of amylose occurs with [iodide] in the range 0.05 -0.5 mM and [amylose rings] in the range 0.3 -1 mM. The required concentrations of both species set limits on possible applications. The incorporation of multiple amylose molecules into matrices was examined by reductive amination of the aldehyde terminus with an amine bearing a cross-linkable group. Subsequent cross-linking afforded molecular architectures albeit in quite low yield. A challenge in this domain concerns purification and characterization of synthetic products. The stability of amylose toward degradation by amylase enzymes was examined in the presence of amylase inhibitors. Taken together, the work establishes the foundation and prospective limits for use of amylose for scavenging iodide.

show abstract

“…Still, there were perceived limitations to the molecular design and/or studies of I : (1) the concentration examined of I was 68 μM, which is likely ∼10 000 fold higher than relevant for radiotherapy; and (2) the enzyme treatment was carried out in Tris–HCl buffer at pH 9.0, which is not physiologically relevant. Several other substrates for EISA strategies were examined, 20–24 yet each proved to have idiosyncratic limitations.…”

Section: Introductionmentioning

confidence: 99%