Endo-N-Acetyl-β-D-Glucosaminidases and Peptide-N4-(N-acetyl-β-D-Glucosaminyl) Asparagine Amidases: More Than Just Tools

Karamanos, Yannis

doi:10.11648/j.ab.20130105.12

Cited by 4 publications

(1 citation statement)

References 189 publications

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“…Endo F3 is known to cleave a wide variety of complex glycans, but not oligomannose and hybrid structures and has 400-fold lower activity on nonfucosylated glycans . Indeed, we found that upon incubation of trastuzumab with endo F3, the majority of glycans was readily removed, but full trimming was not attained, even with large excess of enzyme.…”

Section: Resultsmentioning

confidence: 80%

Chemoenzymatic Conjugation of Toxic Payloads to the Globally Conserved N-Glycan of Native mAbs Provides Homogeneous and Highly Efficacious Antibody–Drug Conjugates

Geel¹,

Wijdeven²,

Heesbeen³

et al. 2015

Bioconjugate Chem.

215

190

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A robust, generally applicable, nongenetic technology is presented to convert monoclonal antibodies into stable and homogeneous ADCs. Starting from a native (nonengineered) mAb, a chemoenzymatic protocol allows for the highly controlled attachment of any given payload to the N-glycan residing at asparagine-297, based on a two-stage process: first, enzymatic remodeling (trimming and tagging with azide), followed by ligation of the payload based on copper-free click chemistry. The technology, termed GlycoConnect, is applicable to any IgG isotype irrespective of glycosylation profile. Application to trastuzumab and maytansine, both components of the marketed ADC Kadcyla, demonstrate a favorable in vitro and in vivo efficacy for GlycoConnect ADC. Moreover, the superiority of the native glycan as attachment site was demonstrated by in vivo comparison to a range of trastuzumab-based glycosylation mutants. A side-by-side comparison of the copper-free click probes bicyclononyne (BCN) and a dibenzoannulated cyclooctyne (DBCO) showed a surprising difference in conjugation efficiency in favor of BCN, which could be even further enhanced by introduction of electron-withdrawing fluoride substitutions onto the azide. The resulting mAb-conjugates were in all cases found to be highly stable, which in combination with the demonstrated efficacy warrants ADCs with a superior therapeutic index.

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Section: Resultsmentioning

confidence: 80%

Chemoenzymatic Conjugation of Toxic Payloads to the Globally Conserved N-Glycan of Native mAbs Provides Homogeneous and Highly Efficacious Antibody–Drug Conjugates

Geel¹,

Wijdeven²,

Heesbeen³

et al. 2015

Bioconjugate Chem.

215

190

View full text Add to dashboard Cite

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A transcriptomic investigation of appetite‐regulation and digestive processes in giant grouper Epinephelus lanceolatus during early larval development

Anderson

Knuckey²,

Cánepa³

et al. 2018

Journal of Fish Biology

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The giant grouper Epinephelus lanceolatus is an ecologically vulnerable species with high market demand. However, efforts to improve larval husbandry are hindered by a lack of knowledge surrounding larval developmental physiology. To address this shortfall, a transcriptomic approach was applied to larvae between 1 and 14 days post hatch (dph) to characterise the molecular ontogenesis of genes that influence appetite and digestion. Appetite regulating factors were detected from 1 dph, including neuropeptide Y, nesfatin-1, cocaine and amphetamine regulated transcript, cholecystokinin and pituitary adenylate cyclase activating peptide and the expression level of several genes changed sharply with the onset of exogenous feeding. The level of expression for proteases, chitinases, lipases and amylases typically followed one of two expression patterns, a general increase as development progressed, or an inverted U-shape with maximal expression at c. 6 dph. Similarly, the tendency among both expression patterns was for the level of expression to increase around the time of mouth-opening. There was also evidence to suggest the presence of putative isoforms for several digestion-related genes. We have provided an insight into appetite-regulation and digestive processes in groupers during early larval development and have developed a transcriptomic database that will aid future efforts to rear this species in an aquaculture setting.

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A divergent synthesis to generate targeted libraries of inhibitors for endo-N-acetylglucosaminidases

et al. 2018

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Cell active inhibitors of glycoside processing enzymes are valuable research tools that help us understand the physiological roles of this diverse class of enzymes. endo-N-Acetylglucosaminidases have gained increased attention for their important roles in both mammals and human pathogens; however, metabolically stable cell active inhibitors of these enzymes are lacking. Here, we describe a divergent synthetic strategy involving elaboration of a thiazoline core scaffold. We illustrate the potential of this approach by using the copper catalysed azide-alkyne click (CuAAC) reaction, in combination with a suitable catalyst to avoid poisoning by the thiazoline moiety, to generate a targeted panel of candidate inhibitors of endo-N-acetylglucosaminidases and chitinases.

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Endo-N-Acetyl-β-D-Glucosaminidases and Peptide-N4-(N-acetyl-β-D-Glucosaminyl) Asparagine Amidases: More Than Just Tools

Cited by 4 publications

References 189 publications

Chemoenzymatic Conjugation of Toxic Payloads to the Globally Conserved N-Glycan of Native mAbs Provides Homogeneous and Highly Efficacious Antibody–Drug Conjugates

Chemoenzymatic Conjugation of Toxic Payloads to the Globally Conserved N-Glycan of Native mAbs Provides Homogeneous and Highly Efficacious Antibody–Drug Conjugates

A transcriptomic investigation of appetite‐regulation and digestive processes in giant grouper Epinephelus lanceolatus during early larval development

A divergent synthesis to generate targeted libraries of inhibitors for endo-N-acetylglucosaminidases

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