Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
Department of Chemistry, University of the Sciences , Philadelphia, Pennsylvania 19104, United States.
J Org Chem. 2017 Dec 15;82(24):13020-13033. doi: 10.1021/acs.joc.7b01956. Epub 2017 Dec 5.
Creating functional macromolecules that possess the diversity and functionality of proteins poses an enormous challenge, as this requires large, preorganized macromolecules to facilitate interactions. Peptoids have been shown to interact with proteins, and combinatorial libraries of peptoids have been useful in discovering new ligands for protein binding. We have created spiroligomer-peptoid hybrids that have a spirocyclic core that preorganizes functional groups in three-dimensional space. By utilizing spiroligomers, we can reduce the number of rotatable bonds between functional groups while increasing the stereochemical diversity of the molecules. We have synthesized 15 new spiroligomer monomer amines that contain two stereocenters and three functional groups (67-84% yields from a common hydantoin starting material) as well as a spiroligomer trimer 25 with six stereocenters and five functional groups. These 16 amines were used to synthesize five first-generation spiroligomer-peptoids hybrids.
设计具有蛋白质多样性和功能性的功能大分子极具挑战性，因为这需要大型的、预先组织好的大分子来促进相互作用。已经证明肽核酸能够与蛋白质相互作用，并且肽核酸的组合文库在发现蛋白质结合的新配体方面非常有用。我们已经合成了螺环寡聚物-肽核酸杂合体，它们具有一个螺环核心，在三维空间中预组织了功能基团。通过利用螺环寡聚物，我们可以减少功能基团之间的可旋转键的数量，同时增加分子的立体化学多样性。我们已经合成了 15 种新的螺环寡聚物单体胺，它们包含两个立体中心和三个功能基团（从常见的海因起始原料获得 67-84%的产率），以及一种具有六个立体中心和五个功能基团的螺环三聚体 25。这 16 种胺被用于合成五种第一代螺环寡聚物-肽核酸杂合体。
