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Dr. Karin Mannerstedt Dr. Narendra Kumar Mishra Dr. Ebbe Engholm Dr. Morten Lundh Dr. Charlotte S. Madsen Dr. Philip J. Pedersen Dr. Priska Le-Huu Dr. Søren L. Pedersen Dr. Nina Buch-Månson Dr. Björn Borgström Dr. Thomas Brimert Dr. Lisbeth N. Fink Dr. Keld Fosgerau Prof. Niels Vrang Prof. Knud J. Jensen 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(9):3166-3176
A glucose responsive insulin (GRI) that responds to changes in blood glucose concentrations has remained an elusive goal. Here we describe the development of glucose cleavable linkers based on hydrazone and thiazolidine structures. We developed linkers with low levels of spontaneous hydrolysis but increased level of hydrolysis with rising concentrations of glucose, which demonstrated their glucose responsiveness in vitro. Lipidated hydrazones and thiazolidines were conjugated to the LysB29 side-chain of HI by pH-controlled acylations providing GRIs with glucose responsiveness confirmed in vitro for thiazolidines. Clamp studies showed increased glucose infusion at hyperglycemic conditions for one GRI indicative of a true glucose response. The glucose responsive cleavable linker in these GRIs allow changes in glucose levels to drive the release of active insulin from a circulating depot. We have demonstrated an unprecedented, chemically responsive linker concept for biopharmaceuticals. 相似文献
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Daniel Lupp Dr. Niels Johan Christensen Dr. Johannes R. Dethlefsen Dr. Peter Fristrup 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(8):3435-3442
The mechanism of the molybdenum‐catalyzed deoxydehydration (DODH) of vicinal diols has been investigated using density functional theory. The proposed catalytic cycle involves condensation of the diol with an MoVI oxo complex, oxidative cleavage of the diol resulting in an MoIV complex, and extrusion of the alkene. We have compared the proposed pathway with several alternatives, and the results have been corroborated by comparison with the molybdenum‐catalyzed sulfoxide reduction recently published by Sanz et al. and with experimental observations for the DODH itself. Improved understanding of the mechanism should expedite future optimization of molybdenum‐catalyzed biomass transformations. 相似文献
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Due to their small size, differential microphone arrays (DMAs) are very attractive. Moreover, they have been effective in combating noise and reverberation. Recently, a new class of DMAs of different orders have been developed with the MacLaurin’s series and the frequency-independent patterns. However, the MacLaurin’s series does not approximate well the exponential function, which appears in the general definition of the beampattern, when the intersensor spacing is not small enough. To circumvent this problem, we propose in this paper to approximate the exponential function with the Jacobi–Anger expansion. Based on this approximation and the frequency-independent Chebyshev patterns, we derive first-, second-, and third-order DMAs. Furthermore, in order to improve the robustness of DMAs against white noise amplification, we propose to use more microphones combined with minimum-norm filters. It is also shown that the Jacobi–Anger expansion is optimal from a mean-squared error perspective. Simulations are carried out to evaluate the performance of the proposed DMAs. 相似文献
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Journal of Radioanalytical and Nuclear Chemistry - 相似文献
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