Sugar Acetonides are a Superior Motif for Addressing the Large, Solvent-Exposed Ribose-33 Pocket of tRNA-Guanine Transglycosylase.
Sugar Acetonides are a Superior Motif for Addressing the Large, Solvent-Exposed Ribose-33 Pocket of tRNA-Guanine Transglycosylase.
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糖丙酮化物是解决 tRNA-鸟嘌呤转糖基酶大、溶剂暴露的核糖 33 袋的优越基序
DOI：
10.1002/chem.201801756
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
F. Diederich
中科院分区：
文献类型：
--
作者：
L. D. Movsisyan;E. Schäfer;A. Nguyen;F. R. Ehrmann;A. Schwab;T. Rossolini;D. Zimmerli;B. Wagner;H. Daff;A. Heine;G. Klebe;F. Diederich
志贺氏菌引起的肠道疾病志贺氏菌病每年影响超过1.2亿 人群。随着对常见抗生素的耐药性出现，对新药的需求非常迫切。细菌tRNA-鸟氨酸转糖基酶(TGT)是控制福氏志贺氏菌致病性的药物靶点。我们报道了从运动发酵单胞菌合成针对TGT核糖-33口袋的糖功能化的林-苯并鸟嘌呤类化合物。用等温滴定量热法和X射线结晶学分析了配体的结合情况。通过改变糖的大小和保护基团来优化口袋占有率。揭示了多环水团簇参与糖基识别的过程。丙酮保护的核糖核糖和呋喃葡萄糖衍生物具有很高的效力，具有结构刚性、良好的溶解性和代谢稳定性。我们得出结论，糖丙酮类化合物在药物开发中具有重要但尚未得到广泛认可的价值。
The intestinal disease shigellosis caused byShigellabacteria affects over 120 million people annually. There is an urgent demand for new drugs as resistance against common antibiotics emerges. Bacterial tRNA‐guanine transglycosylase (TGT) is a druggable target and controls the pathogenicity ofShigella flexneri. We report the synthesis of sugar‐functionalizedlin‐benzoguanines addressing the ribose‐33 pocket of TGT fromZymomonas mobilis. Ligand binding was analyzed by isothermal titration calorimetry and X‐ray crystallography. Pocket occupancy was optimized by variation of size and protective groups of the sugars. The participation of a polycyclic water‐cluster in the recognition of the sugar moiety was revealed. Acetonide‐protected ribo‐ and psicofuranosyl derivatives are highly potent, benefiting from structural rigidity, good solubility, and metabolic stability. We conclude that sugar acetonides have a significant but not yet broadly recognized value in drug development.
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3,4,6-和1,4,6-三甲基-γ-果糖的合成。
影响因子：
15
作者：
T. N. Montgomery
通讯作者：
T. N. Montgomery
用 tRNA-鸟嘌呤转糖基酶 (TGT) 的呋喃糖苷 lin-苯鸟嘌呤配体取代磷酸盐结合位点中的水分子
影响因子：
--
作者：
L.J. Barandun;F.R. Ehrmann;D.Zimmerli;F. Immekus;M. Giroud;C. Grünenfelder;W.B. Schweizer;B. Bernet;M. Betz;A. Heine;G. Klebe;F. Diederich
通讯作者：
F. Diederich
影响因子：
3.2
作者：
REUTER, K;FICNER, R
通讯作者：
FICNER, R
影响因子：
7.3
作者：
Krimmer, Stefan G.;Cramer, Jonathan;Klebe, Gerhard
通讯作者：
Klebe, Gerhard
影响因子：
4
作者：
Immekus, Florian;Barandun, Luzi Jakob;Klebe, Gerhard
通讯作者：
Klebe, Gerhard