Department of Chemistry and Division of Advanced Material Science, Pohang University of Science and Technology (POSTECH), Pohang, South Korea.
Biopolymers. 2019 Jun;110(6):e23289. doi: 10.1002/bip.23289. Epub 2019 May 31.
Peptoids, oligomers of N-substituted glycines, have been attracting increasing interest due to their advantageous properties as peptidomimetics. However, due to the lack of chiral centers and amide hydrogen atoms, peptoids, in general, do not form folding structures except that they have α-chiral side chains. We have recently developed "peptoids with backbone chirality" as a new class of peptoid foldamers called α-ABpeptoids and demonstrated that they could have folding conformations owing to the methyl groups on chiral α-carbons in the backbone structure. Here we report α-ABpeptoid/β -peptide oligomers as a unique peptidomimetic structure with a heterogeneous backbone. This hybrid structure contains a mixed α-ABpeptoid and β -peptide residues arranged in an alternate manner. These α-ABpeptoid/β -peptide oligomers could form intramolecular hydrogen bonding and have better cell permeability relative to pure peptide sequences. These oligomers were shown to adopt ordered folding structures based on circular dichroism studies. Overall, α-ABpeptoid/β -peptide oligomers may represent a novel class of peptidomimetic foldamers and will find a wide range of applications in biomedical and material sciences.
肽缩氨酸是 N-取代甘氨酸的低聚物，由于其作为拟肽的优势特性而引起了越来越多的关注。然而，由于缺乏手性中心和酰胺氢原子，一般来说，除了具有α-手性侧链的肽缩氨酸外，它们不会形成折叠结构。我们最近开发了“具有主链手性的肽缩氨酸”作为一种新的肽缩氨酸类折叠物，称为α-AB 肽缩氨酸，并证明由于主链结构中手性α-碳原子上的甲基，它们可以具有折叠构象。在这里，我们报告了α-AB 肽缩氨酸/β-肽低聚物作为一种具有杂化主链的独特拟肽结构。这种杂化结构包含交替排列的混合α-AB 肽缩氨酸和β-肽残基。这些α-AB 肽缩氨酸/β-肽低聚物可以形成分子内氢键，并且相对于纯肽序列具有更好的细胞通透性。圆二色性研究表明，这些低聚物可以采用有序的折叠结构。总体而言，α-AB 肽缩氨酸/β-肽低聚物可能代表一类新型的拟肽折叠物，并将在生物医学和材料科学领域找到广泛的应用。
