127017-97-4Relevant academic research and scientific papers
Highly efficient synthesis of monodisperse poly(ethylene glycols) and derivatives through macrocyclization of oligo(ethylene glycols)
Zhang, Hua,Li, Xuefei,Shi, Qiuyan,Li, Yu,Xia, Guiquan,Chen, Long,Yang, Zhigang,Jiang, Zhong-Xing
, p. 3763 - 3767 (2015/03/18)
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.
Spacer optimization of new conjugates for a melanoma-selective delivery approach
André, Mathieu,Tarrit, Sébastien,Couret, Marie-Joelle,Galmier, Marie-Josèphe,Débiton, Eric,Chezal, Jean-Michel,Mounetou, Emmanuelle
supporting information, p. 6372 - 6384 (2013/09/23)
In the search for more selective anticancer drugs, we designed and synthesized seven conjugates varying the structure of the linker connecting the 5-iodo-2′-deoxyuridine (IUdR) to the ICF 01012 melanoma-carrier for potential intratumoural specific drug re
Investigation of the origin and synthetic application of the pseudodilution effect for Pd-catalyzed macrocyclisations in concentrated solutions with immobilized catalysts
Brehm, Elisabeth,Breinbauer, Rolf
supporting information, p. 4750 - 4756 (2013/07/26)
Immobilized Pd-complexes allowed macrocyclisations via the Tsuji-Trost-reaction in concentrated solutions. Systematic studies suggest that the origin of this pseudodilution effect is neither film diffusion nor gel diffusion, but the reduction in conformational freedom of intermediates and intramolecular prenucleophile activation. In contrast a pseudodilution effect could not be observed for Sonogashira- and Suzuki-macrocyclisations.
Kinetic stabilization of an oligomeric protein by a single ligand binding event
Wiseman, R. Luke,Johnson, Steven M.,Kelker, Matthew S.,Foss, Ted,Wilson, Ian A.,Kelly, Jeffery W.
, p. 5540 - 5551 (2007/10/03)
Protein native state stabilization imposed by small molecule binding is an attractive strategy to prevent the misfolding and misassembly processes associated with amyloid diseases. Transthyretin (TTR) amyloidogenesis requires rate-limiting tetramer dissociation before misassembly of a partially denatured monomer ensues. Selective stabilization of the native TTR tetramer over the dissociative transition state by small molecule binding to both thyroxine binding sites raises the kinetic barrier of tetramer dissociation, preventing amyloidogenesis. Assessing the amyloidogenicity of a TTR tetramer having only one amyloidogenesis inhibitor (I) bound is challenging because the two small molecule binding constants are generally not distinct enough to allow for the exclusive formation of TTR·I in solution to the exclusion of TTR·I2 and unliganded TTR. Herein, we report a method to tether one fibril formation inhibitor to TTR by disulfide bond formation. Occupancy of only one of the two thyroxine binding sites is sufficient to inhibit tetramer dissociation in 6.0 M urea and amyloidogenesis under acidic conditions by imposing kinetic stabilization on the entire tetramer. The sufficiency of single occupancy for stabilizing the native state of TTR provides the incentive to search for compounds displaying striking negative binding cooperativity (e.g., Kd1 in nanomolar range and Kd2 in the micromolar to millimolar range), enabling lower doses of inhibitor to be employed in the clinic, mitigating potential side effects.
Al2O3/MeSO3H (AMA) as a new reagent with high selective ability for monoesterification of diols
Sharghi, Hashem,Sarvari, Mona Hosseini
, p. 3627 - 3633 (2007/10/03)
A new facile method for monoesterification of diols has been developed. A variety of diols, in particular oligoethylene glycols, were selectively monoesterified in excellent yields by reaction with aromatic and aliphatic acids in the presence of Al2O3/MeSO3H as a new reagent without use of any solvents.
Amplifier molecules for enhancement of diagnosis and therapy
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, (2008/06/13)
Disclosed are amplifier molecules: various organic compounds having branched structures terminating with amine groups to which pharmacologically active groups can be chemically attached. A number of MRI contrast-enhancing agents were synthesized, each comprising plural active groups, such as stable nitroxides and complexes of trivalent metal cations. Such syntheses were successfully performed using a number of amplifiers having different branched structures, demonstrating the general utility of the pertinent chemistry in the synthesis of amplifiers having any of a wide variety of pharmacologically active groups. Amplifiers were also synthesized having linkers terminating with chemically reactive groups such as isothiocyanates, which render the amplifier bifunctional: attachable to polymers, biomacromolecules, or other biocompatible entity possessing multiple reactive sites such as terminal amines. Via such chemistry, the amplifiers are attachable to monoclonal antibodies for concentration of pharmacologically active groups at a desired site in the body.
