DNA mimic helical foldamers with up to 100 units: synthesis and recognition of a multiprotein complex
Abstract
DNA mimic foldamers (DMFOs) are helically folded aromatic oligoamides that mimic the shape and charge distribution of double-stranded B-DNA. DMFOs consist of an alternation of two amino acid monomers, M and Q. Here, we introduce a new synthetic approach of (MQ)n oligomers on solid phase that enabled the production of sequences as long as a 100mer, formally equivalent to a 50-base pair DNA duplex. The approach takes advantage of dimeric Fmoc-MQ-OH as building blocks. Three such macromonomers were synthesized using Q and M units bearing different side chains. Solid phase synthesis protocols were validated in all series. Helix handedness was shown to be determined by a single chiral residue. The purified long oligomers were analyzed by reversed phase HPLC, mass spectrometry, circular dichroism, and nuclear magnetic resonance spectroscopy for their purity, identity, and helix-handedness bias. Clusters of foldamers forming in the presence of Ca2+ could be visualized by cryogenic electron microscopy (cryo-EM). Lastly, a 72mer DMFO was shown to bind to the A-module of the chromatin remodeling complex INO80 slightly tighter than a comparable DNA duplex. A cryo-EM structure of the complex at a resolution of 3.59 Å showed that the DMFO occupies the A-module DNA binding region.
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BibTeX
@article{loos2026mimic,
title = {{DNA mimic helical foldamers with up to 100 units: synthesis and recognition of a multiprotein complex}},
author = {Manuel Loos and Franziska Därr and Céline Douat and Lisa Gourdon-Grünewaldt and Alberto López-Francos and Annika Brem and Karl-Peter Hopfner and Ivan Huc},
journal = {Nucleic Acids Research},
year = {2026},
month = nov,
doi = {10.1093/nar/gkag974},
url = {https://doi.org/10.1093/nar/gkag974},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - DNA mimic helical foldamers with up to 100 units: synthesis and recognition of a multiprotein complex
AU - Manuel Loos
AU - Franziska Därr
AU - Céline Douat
AU - Lisa Gourdon-Grünewaldt
AU - Alberto López-Francos
AU - Annika Brem
AU - Karl-Peter Hopfner
AU - Ivan Huc
PY - 2026
DA - 2026/11/04
JO - Nucleic Acids Research
DO - 10.1093/nar/gkag974
UR - https://doi.org/10.1093/nar/gkag974
AB - DNA mimic foldamers (DMFOs) are helically folded aromatic oligoamides that mimic the shape and charge distribution of double-stranded B-DNA. DMFOs consist of an alternation of two amino acid monomers, M and Q. Here, we introduce a new synthetic approach of (MQ)n oligomers on solid phase that enabled the production of sequences as long as a 100mer, formally equivalent to a 50-base pair DNA duplex. The approach takes advantage of dimeric Fmoc-MQ-OH as building blocks. Three such macromonomers were synthesized using Q and M units bearing different side chains. Solid phase synthesis protocols were validated in all series. Helix handedness was shown to be determined by a single chiral residue. The purified long oligomers were analyzed by reversed phase HPLC, mass spectrometry, circular dichroism, and nuclear magnetic resonance spectroscopy for their purity, identity, and helix-handedness bias. Clusters of foldamers forming in the presence of Ca2+ could be visualized by cryogenic electron microscopy (cryo-EM). Lastly, a 72mer DMFO was shown to bind to the A-module of the chromatin remodeling complex INO80 slightly tighter than a comparable DNA duplex. A cryo-EM structure of the complex at a resolution of 3.59 Å showed that the DMFO occupies the A-module DNA binding region.
SN - 0305-1048
SN - 1362-4962
ER -