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1.
Dr. Sören Kirchgäßner Dr. Michael B. Braun Natascha Bartlick Dr. Cengiz Koç Dr. Christopher D. Reinkemeier Prof. Dr. Edward A. Lemke Prof. Dr. Thilo Stehle Prof. Dr. Dirk Schwarzer 《Angewandte Chemie (International ed. in English)》2023,62(12):e202215460
Lysine acetylation is a charge-neutralizing post-translational modification of proteins bound by bromodomains (Brds). A 1,2,4-triazole amino acid (ApmTri) was established as acetyllysine (Kac) mimic recruiting Brds of the BET family in contrast to glutamine commonly used for simulating this modification. Optimization of triazole substituents and side chain spacing allowed BET Brd recruitment to ApmTri-containing peptides with affinities similar to native substrates. Crystal structures of ApmTri-containing peptides in complex with two BET Brds revealed the binding mode which mirrored that of Kac ligands. ApmTri was genetically encoded and recombinant ApmTri-containing proteins co-enriched BRD3(2) from cellular lysates. This interaction was blocked by BET inhibitor JQ1. With genetically encoded ApmTri, biochemistry is now provided with a stable Kac mimic reflecting charge neutralization and Brd recruitment, allowing new investigations into BET proteins in vitro and in vivo. 相似文献
2.
Deokhee Kang Do-Wook Kim Joo-Chan Kim Prof. Hee-Sung Park 《Angewandte Chemie (International ed. in English)》2023,62(7):e202214815
Demand for peptide-based pharmaceuticals has been steadily increasing, but only limited success has been achieved to date. To expedite peptide-based drug discovery, we developed a general scheme for cell-based screening of cyclic peptide inhibitors armed with a user-designed warhead. We combined unnatural amino acid incorporation and split intein-mediated peptide cyclization techniques and integrated a yeast-based colorimetric screening assay to generate a new scheme that we call the custom-designed warhead-armed cyclic peptide screening platform (CWCPS). This strategy successfully discovered a potent inhibitor, CY5-6Q, that targets human histone deacetylase 8 (HDAC8) with a KD value of 15 nM. This approach can be a versatile and general platform for discovering cyclic peptide inhibitors. 相似文献
3.
三维双材料结构的应力奇异性分析 总被引:1,自引:1,他引:1
应用有限单元法子模型技术,对具有不同界面角的三维双材料结构的应力奇异性进行了分析。结果表明,应用子模型技术估算三维双材料结构的应力奇异性指数是有效的。然后分析了界面端线和界面端点处附近奇异性指数,得到了一些重要而有趣的结果。最后对消除三维双材料结构应力奇异性的几何条件进行了讨论。 相似文献
4.
In this paper we describe an analytic method able to give the multiplication table(s) of the set(s) involved in an S‐expansion process (with either resonance or 0S‐resonant‐reduction) for reaching a target Lie (super)algebra from a starting one, after having properly chosen the partitions over subspaces of the considered (super)algebras. This analytic method gives us a simple set of expressions to find the subset decomposition of the set(s) involved in the process. Then, we use the information coming from both the initial (super)algebra and the target one for reaching the multiplication table(s) of the mentioned set(s). Finally, we check associativity with an auxiliary computational algorithm, in order to understand whether the obtained set(s) can describe semigroup(s) or just abelian set(s) connecting two (super)algebras. We also give some interesting examples of application, which check and corroborate our analytic procedure and also generalize some result already presented in the literature. 相似文献
5.
In this paper, we derive the asymptotic expansions of the moments of normalized partial maxima for general error distribution. A byproduct is to deduce the convergence rates of the moments of normalized maxima to the moments of the corresponding extreme value distribution. 相似文献
6.
7.
A computational and experimental study was conducted to assess the potential of testing waverider configurations in a high-performance,
short-duration expansion tube facility. The tests were performed in the newly commissioned X3 superorbital expansion tube
and provide the first experimental data of a waverider tested at a stagnation enthalpy and equivalent flight speed exceeding
40 MJ/kg and 9 km/s, respectively. Two simple caret configurations were chosen as benchmark test cases to test the use of
the facility, instrumentation and numerical models to investigate these flows. The general performance of the sharp and blunt
leading edge waveriders at angles of attack ranging from 0° to 5° were analyzed and compared to CFD and theoretical predictions.
For the conditions tested, the presence of a strong viscous interaction caused the shock wave to be detached from the leading
edge of the models resulting in a significant loss in performance. An analytical model was developed to account for the strong
coupling between the shock wave and boundary layer. Results were shown to be in very good agreement with CFD estimates for
both configurations at all angles of attack considered. Finite-rate chemistry CFD simulations indicated that real gas effects
other than the residual levels of nonequilibrium freestream dissociation present in the expansion tube flow were negligible
for the conditions tested. The study also revealed that a past flow visualization technique gave a false indication of the
leading edge shock location. An improved experimental visualization technique was successfully tested with results from these
tests correlating well with computational estimates. This study successfully demonstrated the use of the facility to study
waverider performance at speeds representative of orbital flight.
相似文献
8.
力学性能不均匀是焊接接头的三大待征之一,本文采用柔度法研究了不同硬夹层宽度的软夹硬力学不均匀焊接接头疲劳裂纹的闭俣行为。研究结果表明,裂纹尖端附近软区的局部屈服在疲劳载荷卸载过程中促使裂纹闭合。随着硬夹层宽度的减小,这一影响越来越明显。 相似文献
9.
自然形成的岩石节理面的表面形状具有分形特性,利用分形理论来描述岩石节理的粗糙特性,并确立与岩石节理面的剪切力学特性间的关系对于指导岩体工程设计,和管理具有重要一研究利用开发设计的三维激光测距仪在精确测定岩石节理面的表面形状4 基础上,依据变量图法建立了 岩石节理面的 相似文献
10.
黄土构造节理研究及其应用 总被引:3,自引:0,他引:3
作者发现大量不同力学性质的黄土构造节理后,识别了它们的区域性、系统性特征;认定其两组扭裂面代表新构造应力场最大剪切应力方向,利用黄土构造节理系及由其控制的土层沟槽网络恢复了相应地区Q3-4构造应力场;提出构造节理是黄土区地下水运移的主要通道和赋存的场所;发现构造节理是黄土区地裂缝、滑坡、崩塌和水土流失等地质灾害的构造基础之一,证实构造节理是黄土地层的软弱面,风化和继之而来的应力侵蚀就由此开始,进而逐步塑造黄土碟、穴、井、桥、柱、墙、沟等潜蚀地貌和部分侵蚀地貌。研究黄土构造节理对恢复新构造应力场、帮助预测地裂乃至地震活动、控制水土流失和滑塌灾害、进行工程乃至区域稳定性评价、重新认识黄土潜蚀地貌发育规律、指导干旱半干旱黄土区找水,既有理论意义又有实际意义。 相似文献