排序方式: 共有359条查询结果,搜索用时 15 毫秒
31.
Igor Dovgan Alexandre Hentz Oleksandr Koniev Anthony Ehkirch Steve Hessmann Sylvain Ursuegui Sbastien Delacroix Margaux Riomet Frdric Taran Sarah Cianfrani Sergii Kolodych Alain Wagner 《Chemical science》2020,11(5):1210
Controlled protein functionalization holds great promise for a wide variety of applications. However, despite intensive research, the stoichiometry of the functionalization reaction remains difficult to control due to the inherent stochasticity of the conjugation process. Classical approaches that exploit peculiar structural features of specific protein substrates, or introduce reactive handles via mutagenesis, are by essence limited in scope or require substantial protein reengineering. We herein present equimolar native chemical tagging (ENACT), which precisely controls the stoichiometry of inherently random conjugation reactions by combining iterative low-conversion chemical modification, process automation, and bioorthogonal trans-tagging. We discuss the broad applicability of this conjugation process to a variety of protein substrates and payloads.Controlled protein functionalization holds great promise for a wide variety of applications.Applications of protein conjugates are limitless, including imaging, diagnostics, drug delivery, and sensing.1–4 In many of these applications, it is crucial that the conjugates are homogeneous.5 The site-selectivity of the conjugation process and the number of functional labels per biomolecule, known as the degree of conjugation (DoC), are crucial parameters that define the composition of the obtained products and are often the limiting factors to achieving adequate performance of the conjugates. For instance, immuno-PCR, an extremely sensitive detection technique, requires rigorous control of the average number of oligonucleotide labels per biomolecule (its DoC) in order to achieve high sensitivity.6 In optical imaging, the performance of many super-resolution microscopy techniques is directly defined by the DoC of fluorescent tags.7 For therapeutics, an even more striking example is provided by antibody–drug conjugates, which are prescribed for the treatment of an increasing range of cancer indications.8 A growing body of evidence from clinical trials indicates that bioconjugation parameters, DoC and DoC distribution, directly influence the therapeutic index of these targeted agents and hence must be tightly controlled.9Standard bioconjugation techniques, which rely on nucleophile–electrophile reactions, result in a broad distribution of different DoC species (Fig. 1a), which have different biophysical parameters, and consequently different functional properties.10Open in a separate windowFig. 1Schematic representation of the types of protein conjugates.To address this key issue and achieve better DoC selectivity, a number of site-specific conjugation approaches have been developed (Fig. 1b). These techniques rely on protein engineering for the introduction of specific motifs (e.g., free cysteines,11 selenocysteines,12 non-natural amino acids,13,14 peptide tags recognized by specific enzymes15,16) with distinct reactivity compared to the reactivity of the amino acids present in the native protein. These motifs are used to simultaneously control the DoC (via chemo-selective reactions) and the site of payload attachment. Both parameters are known to influence the biological and biophysical parameters of the conjugates,11 but so far there has been no way of evaluating their impact separately.The influence of DoC is more straightforward, with a lower DoC allowing the minimization of the influence of payload conjugation on the properties of the protein substrate. The lowest DoC that can be achieved for an individual conjugate is 1 (corresponding to one payload attached per biomolecule). It is noteworthy that DoC 1 is often difficult to achieve through site-specific conjugation techniques due to the symmetry of many protein substrates (e.g., antibodies). Site selection is a more intricate process, which usually relies on a systematic screening of conjugation sites for some specific criteria, such as stability or reactivity.17Herein, we introduce a method of accessing an entirely new class of protein conjugates with multiple conjugation sites but strictly homogenous DoCs (Fig. 1c). To achieve this, we combined (a) iterative low conversion chemical modification, (b) process automation, and (c) bioorthogonal trans-tagging in one workflow.The method has been exemplified for protein substrates, but it is applicable to virtually any native bio-macromolecule and payload. Importantly, this method allows for the first time the disentangling of the effects of homogeneous DoC and site-specificity on conjugate properties, which is especially intriguing in the light of recent publications revealing the complexity of the interplay between payload conjugation sites and DoC for in vivo efficacy of therapeutic bioconjugates.18 Finally, it is noteworthy that this method can be readily combined with an emerging class of site-selective bioconjugation reagents to produce site-specific DoC 1 conjugates, thus further expanding their potential for biotechnology applications.19 相似文献
32.
Martin Bohner Olga Karpenko Oleksandr Stanzhytskyi 《Journal of Difference Equations and Applications》2013,19(7):1112-1126
In this paper, we present conditions ensuring that solutions of linear second-order differential equations oscillate, provided solutions of corresponding difference equations oscillate. We also establish the converse result, namely, when oscillation of solutions of difference equations implies oscillation of solutions of corresponding differential equations. 相似文献
33.
Sergey V. Ryabukhin Andrey S. Plaskon Semen S. Bondarenko Oleksandr O. Grygorenko Oleg V. Shishkin 《Tetrahedron letters》2010,51(32):4229-812
Chlorotrimethylsilane-promoted Biginelli-type reaction of ethyl 2,4-dioxo-4-phenylbutanoate, benzaldehyde, and various (thio)ureas is explored. The outcome of the reaction depends on the structure of the (thio)urea used and is strongly affected by the acceptor electronic properties of the COOEt substituent in the molecule of the starting β-dicarbonyl compound. The di- and tetrahydropyrimidine derivatives obtained possess two functional groups with orthogonal reactivity, and thus represent promising building blocks for drug discovery. 相似文献
34.
Solozhenko VL Kurakevych OO Sokolov PS Baranov AN 《The journal of physical chemistry. A》2011,115(17):4354-4358
Kinetics of the wurtzite-to-rock-salt transformation in ZnO has been studied in the 5-7 GPa pressure range at temperatures below the activation of diffusion processes. The detailed analysis of non-isothermal experimental data using the general evolution equation describing the kinetics of direct phase transformations in solids allowed us to study the kinetic particularities of both nucleation and growth of the rock-salt phase in parent wurtzite ZnO. The main rate-limiting processes are thermally activated nucleation (E(N) = 383 kJ mol(-1) at 6.9 GPa) and thermally nonactivated (most probably quasi-martensitic) growth (k(G) = 0.833 min(-1) at 6.9 GPa). The high impact of thermal deactivation of nucleation places has been evidenced in the case of slow heating, which indirectly indicates that the rs-ZnO nucleation places are mainly produced by pressure-induced stresses in the parent phase. 相似文献
35.
Oleksandr O. Kurakevych 《高压研究》2013,33(1):48-52
Novel superhard phases are expected to be found among various high-pressure polymorphs of light element compounds. Besides diamond-like phases, the icosahedral boron-rich solids are of particular interest because they could combine high hardness with advanced electronic and phonon transport properties, lightness, high thermal and chemical stability. Here we review some recent results on high-pressure synthesis of novel boron-rich solids. 相似文献
36.
Prof. Dr. Oleksandr O. Grygorenko Prof. Dr. Rostyslav D. Lampeka Prof. Dr. Valentyn A. Chebanov Prof. Dr. Maksym V. Kovalenko Prof. Dr. Stefan Wuttke 《Chemical record (New York, N.Y.)》2024,24(2):e202400008
In this special issue, we highlight recent advances in chemical research by scientists in Ukraine, as well as by their compatriots and collaborators outside the country. Besides spotlighting their contributions, we see our task in fostering global partnerships and multi-, inter-, and trans-disciplinary collaborations, including much-needed co-funded projects and initiatives. The three decades of the renewed Ukraine independence have seen rather limited integration of Ukrainian (chemical) science into global research communities.[1] At the same time, the recent surge of collaborative science initiatives between European Union (EU) and Ukraine echoes the unfolding steps towards Ukraine's full research participation to the Horizon Europe Program. This recently implemented step opens enormous possibilities for Ukrainian researchers to apply for diverse EU research grants. Moreover, a number of journal special issues and collections were launched to highlight Ukrainian chemistry (i. e., by Chemistry of Heterocyclic Compounds[2] and ChemistrySelect[3]). Other scientific initiatives include ‘European Chemistry School for Ukrainians’[4] and ‘Kharkiv Chemical Seminar’[5] as voluntary projects aimed at engaging Ukrainian scientists into European and international chemical research. 相似文献
37.
Irina O. Zhuravel Oleg V. Zaremba Oleksandr S. Detistov Svitlana S. Kovalenko Valentin P. Chernykh 《合成通讯》2013,43(21):3778-3784
New 5-hydroxymethyl-8-methyl-3-(3-aryl-[1,2,4]oxadiazol-5-yl)-2H-pyrano-[2,3-c]pyridin-2-ones and their esters were synthesized. The structure of obtained compounds was determined through a complete 1H NMR analysis. 相似文献
38.
Rusin O St Luce NN Agbaria RA Escobedo JO Jiang S Warner IM Dawan FB Lian K Strongin RM 《Journal of the American Chemical Society》2004,126(2):438-439
The determination of cysteine and homocysteine levels is of great current interest for the monitoring of desease states. A new colorimetric method for the simultaneous detection of l-cysteine and l-homocysteine has been developed. A fluorescein derivative reacts with the above amino acids, producing their respective thiazolidines resulting in color changes. Interference from other amino acids and proteins is minimal. 相似文献
39.
Li F Buchnev O Cheon CI Glushchenko A Reshetnyak V Reznikov Y Sluckin TJ West JL 《Physical review letters》2006,97(14):147801
We investigated the physical properties of low concentration ferroelectric nematic colloids, using calorimetry, optical methods, infrared spectroscopy, and capacitance studies. The resulting homogeneous colloids possess a significantly amplified nematic orientational coupling. We find that the nematic orientation coupling increases by approximately 10% for particle concentrations of 0.2%. A manifestation of the increased orientational order is that the clearing temperature of a nematic colloid increases by up to 40 degrees C compared to the pure liquid crystal host. A theoretical model is proposed in which the ferroelectric particles induce local dipoles whose effective interaction is proportional to the square of the orientational order parameter. 相似文献
40.
We discuss the sensitivity of a population of coupled oscillators to differences in their natural frequencies, i.e., to detuning. We argue that for three or more oscillators, one can get great sensitivity even if the coupling is strong. For N globally coupled phase oscillators we find there can be bifurcation to extreme sensitivity, where frequency locking can be destroyed by arbitrarily small detuning. This extreme sensitivity is absent for N = 2, appears at isolated parameter values for N = 3 and N = 4, and can appear robustly for open sets of parameter values for N > or = 5 oscillators. 相似文献