Department of Chemistry, University of South Florida , 4202 East Fowler Avenue, Tampa, Florida 33620, United States.
College of Chemistry and Chemical Engineering, Central South University , Changsha, Hunan 410083, China.
J Am Chem Soc. 2017 May 31;139(21):7363-7369. doi: 10.1021/jacs.7b03007. Epub 2017 May 16.
New types of foldamer scaffolds are formidably challenging to design and synthesize, yet highly desirable as structural mimics of peptides/proteins with a wide repertoire of functions. In particular, the development of peptidomimetic helical foldamers holds promise for new biomaterials, catalysts, and drug molecules. Unnatural l-sulfono-γ-AApeptides were recently developed and shown to have potential applications in both biomedical and material sciences. However, d-sulfono-γ-AApeptides, the enantiomers of l-sulfono-γ-AApeptides, have never been studied due to the lack of high-resolution three-dimensional structures to guide structure-based design. Herein, we report the first synthesis and X-ray crystal structures of a series of 2:1 l-amino acid/d-sulfono-γ-AApeptide hybrid foldamers, and elucidate their folded conformation at the atomic level. Single-crystal X-ray crystallography indicates that this class of oligomers folds into well-defined right-handed helices with unique helical parameters. The helical structures were consistent with data obtained from solution 2D NMR, CD studies, and molecular dynamics simulations. Our findings are expected to inspire the structure-based design of this type of unique folding biopolymers for biomaterials and biomedical applications.
新型的折叠聚合物支架在设计和合成方面极具挑战性，但作为具有广泛功能的肽/蛋白质结构模拟物却非常理想。特别是，具有类似肽结构的螺旋折叠聚合物的开发有望成为新型生物材料、催化剂和药物分子。最近开发出了非天然的 l-磺酰基-γ-AA 肽，并显示出在生物医学和材料科学领域的潜在应用。然而，由于缺乏高分辨率的三维结构来指导基于结构的设计，d-磺酰基-γ-AA 肽（l-磺酰基-γ-AA 肽的对映异构体）从未被研究过。在此，我们报告了一系列 2:1 l-氨基酸/d-磺酰基-γ-AA 肽杂化折叠聚合物的首次合成和 X 射线晶体结构，并在原子水平上阐明了它们的折叠构象。单晶 X 射线晶体学表明，这类低聚物折叠成具有独特螺旋参数的定义明确的右手螺旋。螺旋结构与从溶液 2D NMR、CD 研究和分子动力学模拟获得的数据一致。我们的发现有望为基于结构设计这种独特折叠生物聚合物用于生物材料和生物医学应用提供启示。
