Right-Handed Helical Foldamers Consisting of De Novo d-AApeptides.
Peng TengNing MaDarrell Cole CerratoFengyu SheTimothy OdomXiang WangLi-June MingArjan van der VaartLukasz WojtasHai XuJianfeng CaiPublished in: Journal of the American Chemical Society (2017)
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.
Keyphrases
- high resolution
- molecular dynamics simulations
- amino acid
- tissue engineering
- molecular docking
- solid state
- mass spectrometry
- high speed
- big data
- tandem mass spectrometry
- electronic health record
- single molecule
- emergency department
- magnetic resonance
- climate change
- machine learning
- human health
- dual energy
- adverse drug
- risk assessment