Stabilising Peptoid Helices Using Non-Chiral Fluoroalkyl Monomers
Diana Gimenez1, Juan A Aguilar1, Elizabeth H C Bromley2
1Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
Angewandte Chemie (International Ed. in English)
|May 31, 2018
Summary
Novel fluoroalkyl monomers control peptoid (peptide-like) secondary structure without chirality or charge. This breakthrough enables new applications in biomaterials and chemical biology by influencing amide bond conformation.
Area of Science:
- Polymer Chemistry
- Chemical Biology
- Biomaterials Science
Background:
- Peptoids offer stability and modular synthesis advantages for chemical biology, medicine, and biomaterials.
- Controlling peptoid secondary structure is challenging due to their tertiary amide backbone lacking hydrogen-bonding capacity.
- Existing methods for conformational control using bulky, charged, or chiral monomers limit broader applications.
Purpose of the Study:
- To investigate non-chiral, neutral fluoroalkyl monomers for controlling peptoid secondary structure.
- To demonstrate the influence of fluoroalkyl monomers on cis/trans amide bond equilibria.
- To design peptoid oligomers with stable helical structures using these novel monomers.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy
- X-ray crystallography
- Model peptoid systems and linear peptoid oligomers
Main Results:
- Fluoroalkyl monomers were shown to influence the cis/trans equilibria of peptoid amide bonds.
- A significant cis-isomer preference was observed, unprecedented without using chirality or charge.
- Novel fluoroalkyl monomers enabled the design of linear peptoid oligomers with stable helical structures.
Conclusions:
- Non-chiral, neutral fluoroalkyl monomers are effective for controlling peptoid conformation.
- This approach overcomes limitations of previous methods, expanding peptoid applications.
- The developed monomers facilitate the creation of peptoid-based helical structures.
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