- Optimization of IEDDA bioorthogonal system: Efficient process to improve trans-cyclooctene/tetrazine interaction
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The antibody pretargeting approach for radioimmunotherapy (RIT) using inverse electron demand Diels-Alder cycloaddition (IEDDA) constitutes an emerging theranostic approach for solid cancers. However, IEDDA pretargeting has not reached clinical trial. The major limitation of the IEDDA strategy depends largely on trans-cyclooctene (TCO) stability. Indeed, TCO may isomerize into the more stable but unreactive cis-cyclooctene (CCO), leading to a drastic decrease of IEDDA efficiency. We have thus developed both efficient and reproducible synthetic pathways and analytical follow up for (PEGylated) TCO derivatives, providing high TCO isomeric purity for antibody modification. We have set up an original process to limit the isomerization of TCO to CCO before the mAbs’ functionalization to allow high TCO/tetrazine cycloaddition.
- Béquignat, Jean-Baptiste,Boucheix, Claude,Canitrot, Damien,Chezal, Jean-Michel,Degoul, Fran?oise,Miot-Noirault, Elisabeth,Moreau, Emmanuel,Navarro-Teulon, Isabelle,Quintana, Mercedes,Rondon, Aurélie,Taiariol, Ludivine,Ty, Nancy
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supporting information
(2020/07/21)
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- Solid Phase Stepwise Synthesis of Polyethylene Glycols
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Polyethylene glycol (PEG) and derivatives with eight and twelve ethylene glycol units were synthesized by stepwise addition of tetraethylene glycol monomers on a polystyrene solid support. The monomer contains a tosyl group at one end and a dimethoxytrityl group at the other. The Wang resin, which contains the 4-benzyloxy benzyl alcohol function, was used as the support. The synthetic cycle consists of deprotonation, Williamson ether formation (coupling), and detritylation. Cleavage of PEGs from solid support was achieved with trifluoroacetic acid. The synthesis including monomer synthesis was entirely chromatography-free. PEG products including those with different functionalities at the two termini were obtained in high yields. The products were analyzed with ESI and MALDI-TOF MS and were found close to monodispersity.
- Khanal, Ashok,Fang, Shiyue
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supporting information
p. 15133 - 15142
(2017/10/31)
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- Highly efficient synthesis of monodisperse poly(ethylene glycols) and derivatives through macrocyclization of oligo(ethylene glycols)
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A macrocyclic sulfate (MCS)-based approach to monodisperse poly(ethylene glycols) (M-PEGs) and their monofunctionalized derivatives has been developed. Macrocyclization of oligo(ethylene glycols) (OEGs) provides MCS (up to a 62-membered macrocycle) as versatile precursors for a range of monofunctionalized M-PEGs. Through iterative nucleophilic ring-opening reactions of MCS without performing group protection and activation, a series of M-PEGs, including the unprecedented 64-mer (2850Da), can be readily prepared. Synthetic simplicity coupled with versatility of this new strategy may pave the way for broader applications of M-PEGs. Macrocycles make synthesis easier: Convenient macrocyclization of the OEGs provides versatile macrocyclic sulfates. These compounds are cornerstones for both monofunctionalization of OEGs and highly efficient synthesis of monodisperse PEGs and derivatives, including an unprecedented 64-mer.
- Zhang, Hua,Li, Xuefei,Shi, Qiuyan,Li, Yu,Xia, Guiquan,Chen, Long,Yang, Zhigang,Jiang, Zhong-Xing
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p. 3763 - 3767
(2015/03/18)
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- Synthesis of poly(ethylene oxide) approaching monodispersity
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Polydispersity in polymers hinders fundamental understanding of their structure-property relationships and prevents them from being used in fields like medicine, where polydispersity affects biological activity. The polydispersity of relatively short-chain poly(ethylene oxide) [(CH 2CH2O2)n; PEO] affects its biological activity, for example, the toxicity and efficacy of PEOylated drugs. As a result, there have been intensive efforts to reduce the dispersity as much as possible (truly monodispersed materials are not possible). Here we report a synthetic procedure that leads to an unprecedented low level of dispersity. We also show for the first time that it is possible to discriminate between PEOs differing in only 1 ethylene oxide (EO) unit, essential in order to verify the exceptionally low levels of dispersity achieved here. It is anticipated that the synthesis of poly(ethylene oxide) approaching monodispersity will be of value in many fields where the applications are sensitive to the distribution of molar mass.
- Maranski, Krzysztof,Andreev, Yuri G.,Bruce, Peter G.
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p. 6411 - 6413
(2014/06/24)
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- A cost-effective, column-free route to ethylene glycol oligomers EG 6, EG10, and EG12
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Although monodisperse ethylene glycol (EG) oligomers are important in a wide range of applications (ranging from drug therapeutics to materials science and engineering), their cost - especially for longer EG oligomers is often prohibitive. For example, decaethylene, EG10, and dodecaethylene, EG12, glycols cost hundreds of dollars per gram, and are only available from most vendors, including Sigma-Aldrich, in the polydispersed form. This high-cost is, in large part, due to laborious nature of synthesis and, above all, purification steps involved. Therefore, the motivation of our work was to design a cost-effective route to the EG oligomers that would altogether avoid the column-chromatography purification. This was achieved by a simple synthetic strategy, which combines bidirectional growth of the EG chains with the protection scheme using easy-to-remove trityl groups. Georg Thieme Verlag Stuttgart · New York.
- Gothard, Chris M.,Grzybowski, Bartosz A.
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p. 717 - 722
(2012/04/04)
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- Convenient multigram synthesis of monodisperse oligo(ethylene glycols): Effective reaction monitoring by infrared spectroscopy using an attenuated total reflection fibre optic probe
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A convenient approach for the synthesis of monodisperse oligo(ethylene glycols) up to 12 units is described. A novel cleavage protocol replacing laborious hydrogenolysis is introduced to achieve a fast, inexpensive and widely applicable procedure. In addition to the synthetic part, Fourier transform infrared (FTIR) spectroscopy using a fibre optic attenuated total reflection (ATR) sensor was applied to monitor the formation of sensitive key intermediates, resulting in optimized reaction times. By applying this in-line technique, the possibility of real-time analysis under inert conditions was impressively demonstrated.
- Lumpi, Daniel,Braunshier, Christian,Hametner, Christian,Horkel, Ernst,Zachhuber, Bernhard,Lendl, Bernhard,Fr?hlich, Johannes
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supporting information; experimental part
p. 6469 - 6471
(2011/02/23)
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- Coupling across a DNA helical turn yields a hybrid DNA/organic catenane doubly tailed with functional termini
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We describe the synthesis of a hybrid DNA/organic macrocycle that is prepared by formation of an amide linkage across one full turn of DNA. Formation of a catenane proved that the linkage crossed a turn rather than running along the phosphodiester backbone contour. The product, a doubly tailed catenane, contains 5′- and 3′-termini that can be functionalized further or used to incorporate the catenane structure into other DNA assemblies. Copyright
- Liu, Yu,Kuzuya, Akinori,Sha, Ruojie,Guillaume, Johan,Wang, Risheng,Canary, James W.,Seeman, Nadrian C.
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supporting information; experimental part
p. 10882 - 10883
(2009/02/05)
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- Synthesis of oligo(ethylene glycol) toward 44-mer
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A synthetic method for oligo(ethylene glycol) toward 44-mer (FW = 1956.35) is described. Reiteration of Williamson's ether synthesis and hydrogenation to remove protecting benzyl group affords desired oligo(ethylene glycol) toward 44-mer in moderate yields. The advantages in this method are use of commercially easily available materials as starting materials and procedures avoiding difficulty in purification of the products as much as possible.
- Ahmed, Saleh A.,Tanaka, Mutsuo
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p. 9884 - 9886
(2007/10/03)
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- An expedient synthesis of monodispersed oligo(ethylene glycols)
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A convenient approach to the synthesis of oligo(ethylene glycols) under phase transfer conditions is described. Oligo(ethylene glycols) (x = 7-12) are obtained in excellent yields and high purity via modular, bi-directional elongation of readily available ethylene glycol bis-tosylates.
- Burkett, Brendan A.,Chan, Tak Hang
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p. 1007 - 1010
(2007/10/03)
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- Preparation and crystallinity of a large unsubstituted crown ether, cyclic heptacosa(oxyethylene) (cyclo-E27, 81-crown-27), studied by Raman spectroscopy, X-ray scattering and differential scanning calorimetry
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Cyclic heptacosa(oxyethyelene) (cyclo-E27, 81-crown-27) was prepared from linear α-hydro, ω-hydroxy-heptacosa(oxyethylene) by reaction with tosyl chloride under alkaline conditions, purified by preparative-scale gel permeation chromatography, and studied by laser-Raman spectroscopy, wide-angle and small-angle X-ray scattering, and differential scanning calorimetry. Comparison was made with the properties of linear oligo(oxyethylene) dimethyl ethers (including C1E27C1). The sub-cell of the crystalline cyclic oligomer was the same as that of its linear counterparts, i.e. the same as that of high-molar-mass poly(oxyethylene). However, the cyclic oligomer crystallised as a twice-folded ring, as confirmed by its long spacing and the frequency of its single-node longitudinal acoustic mode (LAM-1). Enthalpies of fusion and melting temperatures were analysed to provide estimates of the enthalpy and entropy of formation of a fold in an oligo(oxyethylene) layer crystal.
- Yang, Zhuo,Yu, Ga-Er,Cooke, Jennifer,Ali-Adib, Ziad,Viras, Kyriakos,Matsuura, Hiroatsu,Ryan, Anthony J.,Booth, Colin
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p. 3173 - 3182
(2007/10/03)
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- Preparation and characterization of a polyrotaxane consisting of monodisperse poly(ethylene glycol) and α-cyclodextrins
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Here we describe the preparation and characterization of a polyrotaxane consisting of monodisperse α,ω-diaminopoly(ethylene glycol) (28 mer) and α-cyclodextrins (α-CDs). The monodisperse α,ω-diaminopoly(ethylene glycol) was prepared by stepwise synthesis starting from tetrakis(ethylene glycol) coupled with preparative gel permeation chromatography. The complex between α-CDs and α,ω-diaminopoly(ethylene glycol) was treated with 2,4-dinitrofluorobenzene, which is large enough to prevent dethreading. The product was characterized by gel permeation chromatography (GPC) and UV-vis, 1H NMR, 13C NMR, and 2D NOESY NMR spectroscopies. The 1H NMR and 13C NMR spectra show that the product consists of α-CDs, poly(ethylene glycol), and 2,4-dinitrophenyl groups. The 2D NOESY NMR spectra show that a poly(ethylene glycol) chain is included in cavities of α-CDs. The number of α-CDs in a polyrotaxane was determined from the UV-vis and 1H NMR spectra and optical rotation. Twelve α-CDs were found to be captured in a monodisperse poly(ethylene glycol) chain.
- Harada, Akira,Li, Jun,Kamachi, Mikiharu
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p. 3192 - 3196
(2007/10/02)
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