Structure-activity relationship (SAR) by NMR is a technique developed in 1996 by Stephen Fesik at Abbot Laboratories. SAR by NMR is the first experimental demonstration of the fragment-based approach to drug discovery. The method uses NMR spectroscopy to probe the surface area surrounding a protein’s active site for ligand binders. A small ...

2023年9月21日 · We demonstrate our NMR for SAR biophysics strategy with an “undruggable” protein target, HRas, and show the ease with which high-quality μM binders can be developed from an initial ∼7–10 mM fragment screening hit.

1996年11月29日 · A nuclear magnetic resonance (NMR)-based method is described in which small organic molecules that bind to proximal subsites of a protein are identified, optimized, and linked together to produce high-affinity ligands. The approach is called “SAR by NMR” because structure-activity relationships (SAR) are obtained from NMR.

2023年9月21日 · 建立稳健的结构-活性关系 (sar) 是成功药物发现活动的关键，但由于筛选和命中验证工件（误报和漏报），它通常仍然难以捉摸，这常常导致下游时间和资源的无效支出。

SAR-by-NMR 的方法是以靶蛋白为观察对象,利用NMR 技术筛选先导化合物片段,并加以结构改造、优化和化学连接。 SAR-by-NMR 方法的基本原理可. Abbott 实验室的Fesik 小组通过NMR 将上述合理性药物设计和非合理性药物设计 (组合化学)巧妙地结合起来,产生了一种极为有效的发现药物靶分子高亲和性配体的方法,称为SAR-by-NMR [4,5]。 这种新方法结合了合理性设计中的配体设计和优化方法和非合理性设计的合理因素,大大地提高了先导化合物发现的速度和有效性。 原子核 …

1996年11月29日 · A nuclear magnetic resonance (NMR)-based method is described in which small organic molecules that bind to proximal subsites of a protein are identified, optimized, and linked together to produce high-affinity ligands. The approach is called "SAR by NMR" because structure-activity relationships (SAR) are obtained from NMR.

本文介绍了SAR-by-NMR 发现高亲和性配体的基本原理、特点及其在药物发现中的应用。 由于许多药物通过和生物体内的大分子(如蛋白质和核酸) 的选择性结合发挥效用, 因此快速、有效地发现靶分子的高亲和性配体成为各种药物发现方法的首要目标。

To control for differences in the efficiency of reverse transcription of mRNA, we performed cDNA synthesis and subsequent competitive PCR in qua-druplicate. The reaction products were electropho-resed through 2% agarose, visualized by ultraviolet illumination in the presence ofethidium bromide, and quantified by densitometric analysis. 16.

2021年1月26日 · 通过对乙酰羟胺，3′-氰甲基-4-羟基联苯类似物以及基质溶酶的三元配合物的NMR研究，设计合成了11个化合物 (45～55)，生物活性实验证明，与原有单体化合物相比，所有化合物的活性均有增强。 对基质溶酶最具抑制活性的化合物50和53其IC50分别为25和15nM，活性增强近千倍。 图8.基质溶解素抑制剂药物设计概括图.

2022年1月1日 · Structure-activity-relationships (SAR)-by-NMR (Shuker et al. 1996) is originally the appellation of a method for generating systematically high-affinity small molecular weight protein ligands from small molecular fragments in the early stages of drug development.