A click-flipped enzyme substrate boosts the performance of the diagnostic screening for Hunter syndrome

Schwarz, Markus; Skrinjar, Philipp; Fink, Michael; Kronister, Stefan; Mechtler, Thomas P.; Koukos, Panagiotis I.; Bonvin, Alexandre; Kasper, David C.; Mikula, Hannes

doi:10.1039/d0sc04696e

Cited by 2 publications

(2 citation statements)

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“…[35] Among them, 1,4-disubstituted [20] and 1,4,5-trisubstituted 1,2,3-triazole derivatives [36] are significant, as they are found in a large number of biologically and pharmaceutically active molecules that have a broad spectrum of properties such as antibacterial, [20,[36][37][38][39] antiepileptic, [40] antioxidant, [41] antifungal, [42] anticancer agents, [43][44][45][46][47] anti-HIV, [48][49] and other effects. [50] The classical catalytic system for CuAAC reaction is Cu(II) salts along with a reducing agent (sodium ascorbate), [4,[51][52][53][54][55][56][57] which in situ generate the copper(I) ions and usually show good catalytic efficiency. [58][59][60][61][62][63][64][65] Other catalytic systems include metallic copper, [55,66] copper nanoparticles (NPs), [51,56,62] and so on.…”

Section: Introductionmentioning

confidence: 99%

“…CuAAC is a type of Huisgen 1,3‐dipolar cycloaddition based on the formation of 1,2,3‐triazoles between a terminal alkyne and an azide mediated by the copper catalyst [35] . Among them, 1,4‐disubstituted [20] and 1,4,5‐trisubstituted 1,2,3‐triazole derivatives [36] are significant, as they are found in a large number of biologically and pharmaceutically active molecules that have a broad spectrum of properties such as antibacterial, [20,36–39] antiepileptic, [40] antioxidant, [41] antifungal, [42] anticancer agents, [43–47] anti‐HIV, [48–49] and other effects [50] . The classical catalytic system for CuAAC reaction is Cu(II) salts along with a reducing agent (sodium ascorbate), [4,51–57] which in situ generate the copper(I) ions and usually show good catalytic efficiency [58–65] .…”

Section: Introductionmentioning

confidence: 99%

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Thiol‐Functionalized Cellulose Wrapped Copperoxide as a Green Nano Catalyst for Regiospecific Azide‐Alkyne Cycloaddition Reaction: Application in Rufinamide Synthesis

Selim¹,

Neethu²,

Gowri³

et al. 2021

Asian J Org Chem

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In the past few decades, click chemistry (CuAAC reaction) has seen tremendous development both in terms of catalyst designing and method development because 1,2,3triazoles products have shown enormous applications in various fields. The sought after azide-alkyne cycloaddition reaction catalyzed by smaller-sized (~7 nm) Cu(I/II) oxide nanoparticles (Cu I/II O NPs) supported by thiol-functionalized cellulose provided triazole products in excellent yields (90-98%) with remarkable 1,4-regioselectivity, including the 10 g scale synthesis of a rufinamide drug intermediate. The possible reasons for this exceptional activity are the higher ratio of Cu (I), along with the smaller-sized and homogeneously dispersed colloidal nature of Cu I/II O NPs. Most importantly, the reaction underwent industrially friendly greener conditions such as aqueous medium, room temperature, and no additives, etc., suggesting promising for practical applications. The as-prepared catalyst was recycled and reused up to 5 cycles by simply filtering the precipitate 1,2,3-triazoles products without losing significant activity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thiol‐Functionalized Cellulose Wrapped Copperoxide as a Green Nano Catalyst for Regiospecific Azide‐Alkyne Cycloaddition Reaction: Application in Rufinamide Synthesis

Selim¹,

Neethu²,

Gowri³

et al. 2021

Asian J Org Chem

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On the Mechanism of the Lysosomal Enzyme Iduronate‐2‐sulfatase. A Multiscale Approach

Prejanò,

Romeo,

Talerico

et al. 2024

ChemCatChem

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IIduronate‐2‐sulfatase (IDS) is a Ca2+‐dependent enzyme belonging to the family of sulfatases that catalyzes the hydrolysis of sulphurylated glycosaminoglycans (GAGs), like dermatan and heparan sulphate. Its deficiency or modification leads to the accumulation of GAGs in the human body and to the occurrence of severe conditions, such as Hunter’s disease, or Mucopolysaccharidosis type II. Due to its involvement in this syndrome, it is of interest to understand the action mechanism of the enzyme to design new drugs for more efficient medical strategies. In the present work, we carried out a detailed multiscale modelling‐based investigation, adopting molecular dynamics simulation (MDs) and QM/MM calculations to study the enzyme‐dermatan sulfate interactions and to investigate the reaction mechanism of IDS. The analysis of molecular dynamics trajectories helped to shed light on the contribution of the individual residues of the active site in the recognition of dermatan sulfate. The role of FGly84 and His229, investigated in both neutral and protonated states, is highlighted for the binding of the substrate. QM/MM calculations demonstrated that the reaction mechanism is a multistep process occurring via a sulphurylation‐desulphurylation mechanism where the FGly84 first attacks the sulphate group of the dermatan sulphate (DS), and later is desulphurylated.

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A click-flipped enzyme substrate boosts the performance of the diagnostic screening for Hunter syndrome

Abstract: We report on the unexpected finding that click modification of iduronyl azides results in a conformational flip of the pyranose ring, which led to the development of a new strategy...

Cited by 2 publications

References 45 publications

Thiol‐Functionalized Cellulose Wrapped Copperoxide as a Green Nano Catalyst for Regiospecific Azide‐Alkyne Cycloaddition Reaction: Application in Rufinamide Synthesis

Thiol‐Functionalized Cellulose Wrapped Copperoxide as a Green Nano Catalyst for Regiospecific Azide‐Alkyne Cycloaddition Reaction: Application in Rufinamide Synthesis

On the Mechanism of the Lysosomal Enzyme Iduronate‐2‐sulfatase. A Multiscale Approach

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