Department of Chemistry , Durham University , South Road , Durham DH1 3LE , U.K.
Department of Chemistry , Temple University , Philadelphia , Pennsylvania 19122 , United States.
J Am Chem Soc. 2019 Feb 27;141(8):3430-3434. doi: 10.1021/jacs.8b13498. Epub 2019 Feb 15.
Peptoids are peptidomimetics of interest in the fields of drug development and biomaterials. However, obtaining stable secondary structures is challenging, and designing these requires effective control of the peptoid tertiary amide cis/trans equilibrium. Herein, we report new fluorine-containing aromatic monomers that can control peptoid conformation. Specifically, we demonstrate that a fluoro-pyridine group can be used to circumvent the need for monomer chirality to control the cis/trans equilibrium. We also show that incorporation of a trifluoro-methyl group ( NRpe) rather than a methyl group ( NRpe) at the α-carbon of a monomer gives rise to a 5-fold increase in cis-isomer preference.
肽拟似物是药物开发和生物材料领域中引人关注的一类物质。然而，获得稳定的二级结构具有挑战性，并且设计这些结构需要有效地控制肽拟似物的三级酰胺顺/反平衡。在此，我们报告了新的含氟芳香单体，这些单体可控制肽拟似物的构象。具体而言，我们证明可以使用氟代吡啶基团来避免单体手性控制顺/反平衡的需要。我们还表明，在单体的α-碳原子上引入三氟甲基（NRpe）而不是甲基（NRme）会使顺式异构体的偏好增加 5 倍。
