Convenient chemoenzymatic synthesis of β-purine-diphosphate sugars (GDP-fucose-analogues)

Baisch, Gabi; Öhrlein, Reinhold

doi:10.1016/s0968-0896(96)00258-1

Cited by 57 publications

(23 citation statements)

References 21 publications

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“…UDP 3,4,6-Tri-O-acetyl-2-(2′-azido-2′,2′-difluoroacetyl)-)-α-D-galactosamine(12). Monophosphate 11 was coupled to UMP according to the procedure reported by Baisch et al47 Thus, a solution of D-uridine-5′-monophosphate disodium salt (98 mg, 0.266 mmol) in H 2 O (1 mL) was treated with DOWEX 50Wx8 (H + form) for 40 min and filtered. The filtrate was stirred vigorously at r.t. while tributylamine (63 μL, 0.266 mmol) was added dropwise.…”

mentioning

confidence: 99%

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.

218

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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confidence: 99%

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.

218

190

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“…of benzyl alcohol in the presence of triethyl- amine. [17,18] The reference substance 26 was finally obtained by reductive debenzylation of dibenzyl 2,3,4,6-tetra-O-acetyl--mannopyransyl-1-phosphate. The 1 H-31 P NMR COSY spectrum of 26, measured in a TRIS buffer/DMSO solution, shows a cross-peak of 1-H (δ ϭ 5.25 ppm) with Figure 1 1 H-coupled 31 P NMR hydrolysis study of cycloSal-2,3,…”

Section: Hydrolysis Studiesmentioning

confidence: 99%

cycloSaligenyl‐mannose‐1‐monophosphates as a New Strategy in CDG‐Ia Therapy: Hydrolysis, Mechanistic Insights and Biological Activity

et al. 2004

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Phosphomannomutase 2 (PMM-2) deficiency leads to an inefficient intracellular formation of mannose-1-phosphate (1), which causes an inherited metabolic disease with multisystemic abnormalities (Congenital Disorder of Glycosylation type Ia, CDG-Ia). In order to circumvent this metabolic deficiency, the cycloSal approach was applied for the intracellular delivery of mannose-1-monophosphate (1). cycloSaligenyl-pyranose-1-monophosphates 6−11 were obtained by a phosphitylation/oxidation procedure starting from appropriately protected D-pyranoses. The chemical hydrolysis data and the involved hydrolysis mechanisms of cyclosaligenyl-

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“…Finally, a(1-3/4)fucosyl transferase tolerates quite bulky attachments on the 6-position of fucose [33,34]. When the 2-and the 3-OH-group in GDP-fucose are replaced by small substituents [29,30,31], the corresponding sugar nucleotides still act as donors for a(1-3/4)fucosyl transferase.…”

Section: Introductionmentioning

confidence: 99%

Substrate and donor specificity of glycosyl transferases

Ernst¹,

Oehrlein²

1999

Glycotechnology

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It has been shown that all selectins recognize the carbohydrate epitopes sialyl Lewis x and sialyl Lewis a . For the establishment of the structure-activity relationship, the efficient synthesis of these tetrasaccharides and derivatives is therefore of vital interest. The glycosyl transferase-mediated approach is summarized with emphasis on the use of modified acceptors and modified sugar-nucleotide donors. A survey of the involved enzymes: b(1-3) and b(1-4)galactosyl transferases, a(2-3)sialyl transferase, FucT III and FucT VI reveals that the enzymatic synthesis is highly efficient for the rapid preparation of sialyl Lewis x -and sialyl Lewis a -derivatives.

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Convenient chemoenzymatic synthesis of β-purine-diphosphate sugars (GDP-fucose-analogues)

Cited by 57 publications

References 21 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

cycloSaligenyl‐mannose‐1‐monophosphates as a New Strategy in CDG‐Ia Therapy: Hydrolysis, Mechanistic Insights and Biological Activity

Substrate and donor specificity of glycosyl transferases

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