Cytosine-Rich DNA Aptamers Reveal Recognition Principles for Structurally Diverse Lipopolysaccharides.
- 1Kirin Central Research Institute, Kirin Holdings Company, Ltd., Fujisawa, Kanagawa 251-8555, Japan.
Abstract
Lipopolysaccharides (LPS) are structurally heterogeneous glycolipids whose variable composition and supramolecular organization challenge the design of analytical recognition elements. Here, independent magnetic bead-based SELEX against four LPS preparations yielded three cytosine-rich DNA aptamers that bound five structurally distinct LPS preparations, including both O-antigen-containing and O-antigen-deficient forms, with nanomolar apparent dissociation constants. Mutational analysis showed that disruption of the native C-rich sequence architecture strongly impaired binding, and the repeated emergence of such motifs across independent selections points to an underexplored sequence solution for LPS recognition. UV melting and native PAGE showed acidic pH-induced i-motif-like transitions, whereas binding was maximal at neutral pH, indicating that the acidic folded state is not the functional recognition conformation. Comparisons across immobilization formats, component competition assays with isolated lipid A and free Kdo, and biolayer interferometry with isolated lipid A indicate that recognition is not explained by isolated lipid A or free Kdo alone but is instead consistent with intact LPS presentation in a core-proximal context under the assay conditions. Together, these results reveal recognition principles that link cytosine-rich sequence motifs, pH-dependent folding, target presentation, and core-proximal LPS features in the analytical molecular recognition of heterogeneous LPS.
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BibTeX
@article{tatsumi2026cytosinerich,
title = {{Cytosine-Rich DNA Aptamers Reveal Recognition Principles for Structurally Diverse Lipopolysaccharides.}},
author = {Atsuro Tatsumi and Natsuka Koyama and Makoto Yamashita},
journal = {ACS measurement science au},
year = {2026},
month = aug,
doi = {10.1021/acsmeasuresciau.6c00157},
url = {https://europepmc.org/article/MED/42921466},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Cytosine-Rich DNA Aptamers Reveal Recognition Principles for Structurally Diverse Lipopolysaccharides.
AU - Atsuro Tatsumi
AU - Natsuka Koyama
AU - Makoto Yamashita
PY - 2026
DA - 2026/08/10
JO - ACS measurement science au
DO - 10.1021/acsmeasuresciau.6c00157
UR - https://europepmc.org/article/MED/42921466
AB - Lipopolysaccharides (LPS) are structurally heterogeneous glycolipids whose variable composition and supramolecular organization challenge the design of analytical recognition elements. Here, independent magnetic bead-based SELEX against four LPS preparations yielded three cytosine-rich DNA aptamers that bound five structurally distinct LPS preparations, including both O-antigen-containing and O-antigen-deficient forms, with nanomolar apparent dissociation constants. Mutational analysis showed that disruption of the native C-rich sequence architecture strongly impaired binding, and the repeated emergence of such motifs across independent selections points to an underexplored sequence solution for LPS recognition. UV melting and native PAGE showed acidic pH-induced i-motif-like transitions, whereas binding was maximal at neutral pH, indicating that the acidic folded state is not the functional recognition conformation. Comparisons across immobilization formats, component competition assays with isolated lipid A and free Kdo, and biolayer interferometry with isolated lipid A indicate that recognition is not explained by isolated lipid A or free Kdo alone but is instead consistent with intact LPS presentation in a core-proximal context under the assay conditions. Together, these results reveal recognition principles that link cytosine-rich sequence motifs, pH-dependent folding, target presentation, and core-proximal LPS features in the analytical molecular recognition of heterogeneous LPS.
SN - 2694-250X
ER -