---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '22012'
abstract:
- lang: eng
text: Single stranded helically folded aromatic oligoamides bearing anionic phosphonate
side chains have been shown to bind to some DNA-binding proteins better than DNA
itself. However, these DNA mimic foldamers have until now mainly consisted of
a single repeat motif, like a poly(dA:dT) DNA duplex, and contained limited sequence
information. Here, we introduce new monomers designed to display different chemical
functionalities in the major groove of the DNA mimics. Four new Fmoc-protected
amino acid monomers have been synthesized and incorporated into oligomers. Sixteen
foldamer sequences were prepared on solid phase. Their conformation in solution
and in the solid state and their conformational dynamics were investigated using
NMR, circular dichroism, molecular modeling, and X-ray crystallography. The results
show that three of four new monomers behaved as designed, and that their introduction
enhances the conformational dynamics of the DNA mimic foldamers. In a fourth case,
conformational behavior proved to be more complex than expected. The modified
sequences retained an ability to bind to bacterial histone-like protein HU. These
results showcase design strategies to manipulate large molecular biomimetics where
not only side chains but also main chain components are varied. The new monomers
pave the way to complex DNA mimic foldamer sequences targeting proteins that recognize
sequence-selective DNA-binding proteins such as transcription factors or restriction
enzymes.
acknowledgement: We acknowledge financial support from the European Research Council
(ERC) under the European Union's Horizon Europe Framework Programme (grant agreement
no. ERC-2021-ADG-320892) and from the China Scholarship Council (CSC, predoctoral
fellowship to J. W.). We thank L. Allmendinger for assistance with NMR measurements,
P. Mayer for his assistance in solving the crystal structures of 1 and 1d, L. Bodero
for assistance with automated solid-phase synthesis, M. Rogovoi for providing monomer
precursors, and M. Loos for the purification and analysis of compounds 15a–19a.
We thank M. Soler-Lopez (ID23-1, ESRF, Grenoble) and I. Bento (EMBL P13, Petra III,
DESY, Hamburg) for assistance during data collection at the synchrotron beamlines.
article_processing_charge: Yes
article_type: original
author:
- first_name: Jiaojiao
full_name: Wu, Jiaojiao
last_name: Wu
- first_name: Valentina
full_name: Corvaglia, Valentina
last_name: Corvaglia
- first_name: Tulika
full_name: Chakrabortty, Tulika
last_name: Chakrabortty
- first_name: Pradeep K
full_name: Mandal, Pradeep K
id: 6a3def15-d4b4-11ef-9fa9-a24c1f545ec3
last_name: Mandal
orcid: 0000-0001-5996-956X
- first_name: Ivan
full_name: Huc, Ivan
last_name: Huc
citation:
ama: Wu J, Corvaglia V, Chakrabortty T, Mandal PK, Huc I. Tailoring the major groove
of DNA mimic foldamers. Chemical Science. 2026;17(32):15479–15489. doi:10.1039/d6sc00798h
apa: Wu, J., Corvaglia, V., Chakrabortty, T., Mandal, P. K., & Huc, I. (2026).
Tailoring the major groove of DNA mimic foldamers. Chemical Science. Royal
Society of Chemistry. https://doi.org/10.1039/d6sc00798h
chicago: Wu, Jiaojiao, Valentina Corvaglia, Tulika Chakrabortty, Pradeep K Mandal,
and Ivan Huc. “Tailoring the Major Groove of DNA Mimic Foldamers.” Chemical
Science. Royal Society of Chemistry, 2026. https://doi.org/10.1039/d6sc00798h.
ieee: J. Wu, V. Corvaglia, T. Chakrabortty, P. K. Mandal, and I. Huc, “Tailoring
the major groove of DNA mimic foldamers,” Chemical Science, vol. 17, no.
32. Royal Society of Chemistry, pp. 15479–15489, 2026.
ista: Wu J, Corvaglia V, Chakrabortty T, Mandal PK, Huc I. 2026. Tailoring the major
groove of DNA mimic foldamers. Chemical Science. 17(32), 15479–15489.
mla: Wu, Jiaojiao, et al. “Tailoring the Major Groove of DNA Mimic Foldamers.” Chemical
Science, vol. 17, no. 32, Royal Society of Chemistry, 2026, pp. 15479–15489,
doi:10.1039/d6sc00798h.
short: J. Wu, V. Corvaglia, T. Chakrabortty, P.K. Mandal, I. Huc, Chemical Science
17 (2026) 15479–15489.
das_tickbox: '1'
dataavailabilitystatement: "CCDC 2514117, 2514118, 2286782 and 2478322 (compound 1,
compound 1d, oligomer 5, and oligomer 6, respectively) contain the supplementary
crystallographic data for this paper.54a–d \r\n\r\nThe supporting data have been
provided as part of the supplementary information (SI). Supplementary information:
SI figures, detailed experimental protocols, crystallographic studies, and characterisation
of new compounds. See DOI: https://doi.org/10.1039/d6sc00798h."
date_created: 2026-06-16T08:04:15Z
date_published: 2026-08-19T00:00:00Z
date_updated: 2026-10-19T08:35:08Z
day: '19'
ddc:
- '540'
department:
- _id: LifeSc
doi: 10.1039/d6sc00798h
external_id:
pmid:
- '42388815'
file:
- access_level: open_access
checksum: fee032060eb71cba73afa8e301b9ee94
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creator: dernst
date_created: 2026-10-19T08:32:00Z
date_updated: 2026-10-19T08:32:00Z
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fulldoi: https://doi.org/10.1039/d6sc00798h
has_accepted_license: '1'
intvolume: ' 17'
issue: '32'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 15479–15489
pmid: 1
publication: Chemical Science
publication_identifier:
eissn:
- 2041-6539
issn:
- 2041-6520
publication_status: published
publisher: Royal Society of Chemistry
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Tailoring the major groove of DNA mimic foldamers
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2026'
...