亲脂性
扁桃体
化学
刚度(电磁)
结构刚度
侧链
分子动力学
磁导率
脚手架
广告
立体化学
生物物理学
膜
组合化学
计算化学
有机化学
肽
材料科学
体外
生物化学
计算机科学
聚合物
生物
几何学
复合材料
数学
数据库
作者
Akihiro Furukawa,Joshua Schwochert,Cameron R. Pye,Daigo Asano,Quinn Edmondson,Alexandra C. Turmon,Victoria Klein,Satoshi Ono,Okimasa Okada,R. Scott Lokey
标识
DOI:10.1002/anie.202004550
摘要
Abstract Large macrocyclic peptides can achieve surprisingly high membrane permeability, although the properties that govern permeability in this chemical space are only beginning to come into focus. We generated two libraries of cyclic decapeptides with stable cross‐β conformations, and found that peptoid substitutions within the β‐turns of the macrocycle preserved the rigidity of the parent scaffold, whereas peptoid substitutions in the opposing β‐strands led to “chameleonic” species that were rigid in nonpolar media but highly flexible in water. Both rigid and chameleonic compounds showed high permeability over a wide lipophilicity range, with peak permeabilities differing significantly depending on scaffold rigidity. Our findings indicate that modulating lipophilicity can be used to engineer favorable ADME properties into both rigid and flexible macrocyclic peptides, and that scaffold rigidity can be used to tune optimal lipophilicity.
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