排序方式: 共有69条查询结果,搜索用时 593 毫秒
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Nitin J. Pawar Lei Wang Takuya Higo Chandrabali Bhattacharya Pavan K. Kancharla Fuming Zhang Kedar Baryal Chang‐Xin Huo Jian Liu Robert J. Linhardt Xuefei Huang Linda C. Hsieh‐Wilson 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(51):18750-18756
The complex sulfation motifs of heparan sulfate glycosaminoglycans (HS GAGs) play critical roles in many important biological processes. However, an understanding of their specific functions has been hampered by an inability to synthesize large numbers of diverse, yet defined, HS structures. Herein, we describe a new approach to access the four core disaccharides required for HS/heparin oligosaccharide assembly from natural polysaccharides. The use of disaccharides rather than monosaccharides as minimal precursors greatly accelerates the synthesis of HS GAGs, providing key disaccharide and tetrasaccharide intermediates in about half the number of steps compared to traditional strategies. Rapid access to such versatile intermediates will enable the generation of comprehensive libraries of sulfated oligosaccharides for unlocking the “sulfation code” and understanding the roles of specific GAG structures in physiology and disease. 相似文献
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Takayoshi Tsuzuki Natsumi Sakaguchi Takashi Kudoh Satoshi Takano Masato Uehara Takashi Murayama Takashi Sakurai Minako Hashii Haruhiro Higashida Karin Weber Andreas H. Guse Tomoshi Kameda Takatsugu Hirokawa Yasuhiro Kumaki Barry V. L. Potter Hayato Fukuda Mitsuhiro Arisawa Satoshi Shuto 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2013,125(26):6765-6769
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Nikolaj S. Troelsen Elena Shanina Diego Gonzalez-Romero Daniela Danková Ida S. A. Jensen Katarzyna J. Śniady Faranak Nami Hengxi Zhang Christoph Rademacher Ana Cuenda Charlotte H. Gotfredsen Mads H. Clausen 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(6):2224-2230
Fragment-based drug discovery (FBDD) is a popular method in academia and the pharmaceutical industry for the discovery of early lead candidates. Despite its wide-spread use, the approach still suffers from laborious screening workflows and a limited diversity in the fragments applied. Presented here is the design, synthesis, and biological evaluation of the first fragment library specifically tailored to tackle both these challenges. The 3F library of 115 fluorinated, Fsp3-rich fragments is shape diverse and natural-product-like with desirable physicochemical properties. The library is perfectly suited for rapid and efficient screening by NMR spectroscopy in a two-stage workflow of 19F NMR and subsequent 1H NMR methods. Hits against four diverse protein targets are widely distributed among the fragment scaffolds in the 3F library and a 67 % validation rate was achieved using secondary assays. This collection is the first synthetic fragment library tailor-made for 19F NMR screening and the results demonstrate that the approach should find broad application in the FBDD community. 相似文献
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