elements

Macrocycles are promising scaffolds for the design of novel RNA targeting molecules. This collection of macrocycles for RNA consists of very diverse, drug-like molecules which incorporate certain known RNA-recognition elements (e.g. nucleobase ring systems and analogs) distributed within macrocyclic rings or peripheral fragments. As macrocyclic molecules tend to be larger than traditional screening molecules, it is vital to carefully assess and control their physicochemical properties. All macrocycles have been tested for aqueous and DMSO solubility with cutoffs applied at 10 mM in DMSO and 50 µM in PBS (pH 7.4); PAMPA permeability has also been tested for representative set of macrocycles.

“BioDesign” approach incorporates key structural features of known pharmacologically relevant natural products (e.g. alkaloids and other secondary metabolites) into synthetically feasible medicinal chemistry scaffolds. In order to identify the privileged pharmacophores, ring systems and linkers, we have carried out statistical analysis of structural features of natural products, marketed drugs, and drug candidates.

Saturated, fused ring, spiro, and bridged systems with a tendency towards multiple chiral centers are highly privileged among natural products and marketed drugs yet these structures are very poorly represented in commercial libraries. This library addressed this market need by incorporating these privileged elements into the design of novel synthetic molecules with high molecular framework diversity, multiple stereogenic centers (≥2), and degree of saturation (Fsp3 > 0.5).

拟肽化合物是一类药效团在三维空间中模拟天然肽或蛋白质，并保留与生物靶标相互作用的能力，产生相同的生物效应的化合物。拟肽化合物的设计是为了规避一些天然肽自身存在的问题：如对蛋白水解作用的稳定性(活性持续时间)和较差的生物利用度，某些其他性质，如受体的选择性或效能，往往可以得到很大的改善。拟肽的设计和合成是非常重要的，因为在分子识别和信号传递中，尤其是在生命系统中，肽和蛋白-蛋白相互作用起着主导作用。因此，拟肽类化合物在新药开发中具有巨大潜力。

MCE 拟肽类化合物库包含 376 种小分子化合物，包括类肽，α-螺旋类似物，β-折叠类似物等，是药物发现中研究构效关系不可或缺的工具。