TY - JOUR

T1 - Triangular prism-shaped β-peptoid helices as unique biomimetic scaffolds

AU - Laursen, Jonas S

AU - Harris, Pernille

AU - Fristrup, Peter

AU - Olsen, Christian A

PY - 2015

Y1 - 2015

N2 - β-Peptoids are peptidomimetics based on N-alkylated β-aminopropionic acid residues (or N-alkyl-β-alanines). This type of peptide mimic has previously been incorporated in biologically active ligands and has been hypothesized to be able to exhibit foldamer properties. Here we show, for the first time, that β-peptoids can be tuned to fold into stable helical structures. We provide high-resolution X-ray crystal structures of homomeric β-peptoid hexamers, which reveal right-handed helical conformations with exactly three residues per turn and a helical pitch of 9.6-9.8 Å between turns. The presence of folded conformations in solution is supported by circular dichroism spectroscopy showing length- and solvent dependency, and molecular dynamics simulations provide further support for a stabilized helical secondary structure in organic solvent. We thus outline a framework for future design of novel biomimetics that display functional groups with high accuracy in three dimensions, which has potential for development of new functional materials.

AB - β-Peptoids are peptidomimetics based on N-alkylated β-aminopropionic acid residues (or N-alkyl-β-alanines). This type of peptide mimic has previously been incorporated in biologically active ligands and has been hypothesized to be able to exhibit foldamer properties. Here we show, for the first time, that β-peptoids can be tuned to fold into stable helical structures. We provide high-resolution X-ray crystal structures of homomeric β-peptoid hexamers, which reveal right-handed helical conformations with exactly three residues per turn and a helical pitch of 9.6-9.8 Å between turns. The presence of folded conformations in solution is supported by circular dichroism spectroscopy showing length- and solvent dependency, and molecular dynamics simulations provide further support for a stabilized helical secondary structure in organic solvent. We thus outline a framework for future design of novel biomimetics that display functional groups with high accuracy in three dimensions, which has potential for development of new functional materials.

KW - Biomimetic Materials

KW - Circular Dichroism

KW - Crystallography, X-Ray

KW - Drug Design

KW - Isomerism

KW - Molecular Dynamics Simulation

KW - Peptoids

KW - Protein Folding

KW - Protein Multimerization

KW - Protein Structure, Secondary

KW - Spectrometry, Fluorescence

KW - Structure-Activity Relationship

KW - Tissue Scaffolds

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ncomms8013

DO - 10.1038/ncomms8013

M3 - Journal article

C2 - 25943784

VL - 6

SP - 1

EP - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 7013

ER -