Modular Synthesis of Bifunctional Linkers for Materials Science

Moreau, J.M.; Marchand‐Brynaert, Jacqueline

doi:10.1002/ejoc.201001666

Cited by 9 publications

(14 citation statements)

References 30 publications

(17 reference statements)

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“…N -Demethylation of 1 using 1-chloroethyl chloroformate (ACE-Cl) followed by methanolysis gave the nor-compound, 5 . As shown in Scheme , alkylation of 5 with the PEG 3 -linker ( 6 ) gave the PEGylated compound 8 . In situ deprotection with TFA and coupling of 6-carboxy-JF 549 or 6-carboxy-JF 646 with 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride (EDC·HCl) and hydroxybenzotriazole (HOBt) gave 3 and DG3-63 ( 10 ), respectively.…”

Section: Resultsmentioning

confidence: 99%

“…In situ deprotection with TFA and coupling of 6-carboxy-JF 549 or 6-carboxy-JF 646 with 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride (EDC·HCl) and hydroxybenzotriazole (HOBt) gave 3 and DG3-63 ( 10 ), respectively. In a similar manner described for 3 and 10 , a longer PEG linked analogue was prepared, by alkylation of 5 with the PEG 6 -linker ( 7 ) to give 9 , which was then deprotected with TFA, followed by EDC/HOBt-coupling with 6-carboxy-JF 646 to afford 4 , the PEG 6 version of fluorescent cocaine analogue 10 . A piperazine-based linker was also prepared based on an earlier fluorescent analogue of 1 (unpublished data).…”

Section: Resultsmentioning

confidence: 99%

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Novel Fluorescent Ligands Enable Single-Molecule Localization Microscopy of the Dopamine Transporter

Guthrie

Herenbrink

Lycas

et al. 2020

ACS Chem. Neurosci.

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The dopamine transporter (DAT) is critical for spatiotemporal control of dopaminergic neurotransmission and is the target for therapeutic agents, including ADHD medications, and abused substances, such as cocaine. Here, we develop new fluorescently labeled ligands that bind DAT with high affinity and enable single-molecule detection of the transporter. The cocaine analogue MFZ2-12 (1) was conjugated to novel rhodamine-based Janelia Fluorophores (JF 549 and JF 646 ). High affinity binding of the resulting ligands to DAT was demonstrated by potent inhibition of [ 3 H]dopamine uptake in DAT transfected CAD cells and by competition radioligand binding experiments on rat striatal membranes. Visualization of binding was substantiated by confocal or TIRF microscopy revealing selective binding of the analogues to DAT transfected CAD cells. Single particle tracking experiments were performed with JF 549 -conjugated DG3-80 (3) and JF 646conjugated DG4-91 (4) on DAT transfected CAD cells enabling quantification and categorization of the dynamic behavior of DAT into four distinct motion classes (immobile, confined, Brownian, and directed). Finally, we show that the ligands can be used in direct stochastic optical reconstruction microscopy (dSTORM) experiments permitting further analyses of DAT distribution on the nanoscale. In summary, these novel fluorescent ligands are promising new tools for studying DAT localization and regulation with single-molecule resolution.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Novel Fluorescent Ligands Enable Single-Molecule Localization Microscopy of the Dopamine Transporter

Guthrie

Herenbrink

Lycas

et al. 2020

ACS Chem. Neurosci.

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“…Several syntheses of aminoalcohols derived from oligoethylene glycol have been reported. [47][48][49] Using a slightly modified approach, tetraethylene glycol (7) was first converted to the mono-tosylate 8 via reaction with tosyl chloride in pyridine in a 75% yield. The remaining free hydroxyl was then protected as the corresponding TBDPS silyl ether via reaction with tert-butyldiphenylsilyl chloride (TBDPS-Cl) and imidazole in dichloromethane at 0 8C to yield 9 in 97% yield.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of a TLR4 Agonist‐Carbohydrate Antigen Conjugate As A Self‐Adjuvanting Cancer Vaccine

2016

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Tumour‐associated carbohydrate antigens (TACAs) are promising targets for therapeutic cancer vaccination efforts. However, an inherent limitation of this approach is the poor immunogenicity of carbohydrate epitopes. In an effort to overcome this problem, a self‐adjuvanting TACA has been targeted and synthesized herein, in which a Toll‐like receptor 4 activating lipid A mimic is employed as an immunostimulant and covalently linked to a broadly expressed TACA, the Thomsen‐Freidenreich (TF) antigen. Individual components were first prepared, including the lipid A mimic, the Galβ(1‐3)GalNAc disaccharide building block, and the tetraethylene glycol‐derived linker. The linker was then coupled with the TF disaccharide, and then with the lipid A mimic, both under HBTU‐mediated peptide coupling condition, to provide the conjugated precursor. Global debenzylation via catalytic hydrogenation afforded the designed self‐adjuvanting TF antigen in overall good yield.

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“…Triethylene Glycol Urea 13c. Compound 13c was prepared according to the general procedure for synthesis of substituted ureas using 2-(2-(2-aminoethoxy)ethoxy)ethan-1-ol 23 (455 mg, 3.05 mmol, 1.00 equiv). After 24 h, the crude residue was purified by flash column chromatography on silica gel (eluent: 40 → 100% ethyl acetate in hexanes) to afford triethylene glycol urea 13c (1.47 g, 84%) as a white solid.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Synthesis and Evaluation of Agelastatin Derivatives as Potent Modulators for Cancer Invasion and Metastasis

Antropow

Xu²,

Buchsbaum³

et al. 2017

J. Org. Chem.

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The synthesis of new agelastatin alkaloid derivatives and their anticancer evaluation in the context of the breast cancer microenvironment is described. A variety of N1-alkyl and C5-ether agelastatin derivatives were accessed via application of our strategy for convergent imidazolone synthesis from a common thioester along with appropriately substituted urea and alcohol components. These agelastatin derivatives were evaluated in our three-dimensional co-culture assay for the effects of mammary fibroblasts on associated breast cancer cells. We have discovered that agelastatin alkaloids are potent modulators for cancer invasion and metastasis at non-cytotoxic doses. Herein we discuss the increased potency of (−)-agelastatin E as compared to (−)-agelastatin A in this capacity, in addition to identification of new agelastatin derivatives with activity that is statistically equivalent to (−)-agelastatin E. The chemistry described in this report provides a platform for the rapid synthesis of agelastatin derivatives with excellent potency (50–100 nM) as modulators for cancer invasion and metastasis.

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Modular Synthesis of Bifunctional Linkers for Materials Science

Cited by 9 publications

References 30 publications

Novel Fluorescent Ligands Enable Single-Molecule Localization Microscopy of the Dopamine Transporter

Novel Fluorescent Ligands Enable Single-Molecule Localization Microscopy of the Dopamine Transporter

Synthesis of a TLR4 Agonist‐Carbohydrate Antigen Conjugate As A Self‐Adjuvanting Cancer Vaccine

Synthesis and Evaluation of Agelastatin Derivatives as Potent Modulators for Cancer Invasion and Metastasis

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