Strengthening an Intramolecular Non‐Classical Hydrogen Bond to Get in Shape for Binding DOI Creative Commons
Norbert Varga, Martin Smieško, Xiaohua Jiang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: July 27, 2024

Abstract In this research article, we report on the strengthening of a non‐classical hydrogen bond (C−H⋅⋅⋅O) by introducing electron withdrawing groups at carbon atom. The approach is demonstrated example derivatives physiological E‐selectin ligand sialyl Lewis x ( 1 , sLe ). Its affinity mainly due to beneficial entropy term, which predominantly caused pre‐organization in its binding conformation. We have shown, that among elements responsible for pre‐organization, stabilization between H−C5 l ‐fucose and ring oxygen O5 neighboring d ‐galactose moiety essential yields 7.4 kJ mol −1 . This effect could be further strengthened replacing 6,6,6‐trifluoro‐ leading an improved H‐bond 14.9 i.e., bioactive For series glycomimetics ), outcome confirmed high field NMR‐shifts Fuc X‐ray diffraction analysis co‐crystallized with as well isothermal titration calorimetry. Furthermore, electron‐withdrawing character CF 3 ‐group beneficially influences pharmacokinetic properties mimetics. Thus, acid‐stability, prerequisite gastrointestinal stability, substantially improved.

Language: Английский

NMR investigations of glycan conformation, dynamics, and interactions DOI
Jesús Angulo, Ana Ardá, Sara Bertuzzi

et al.

Progress in Nuclear Magnetic Resonance Spectroscopy, Journal Year: 2024, Volume and Issue: 144-145, P. 97 - 152

Published: Oct. 12, 2024

Language: Английский

Citations

4
Strengthening an Intramolecular Non‐Classical Hydrogen Bond to Get in Shape for Binding DOI Creative Commons
Norbert Varga, Martin Smieško, Xiaohua Jiang

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(42)

Published: July 27, 2024

Abstract In this research article, we report on the strengthening of a non‐classical hydrogen bond (C−H⋅⋅⋅O) by introducing electron withdrawing groups at carbon atom. The approach is demonstrated example derivatives physiological E‐selectin ligand sialyl Lewis x ( 1 , sLe ). Its affinity mainly due to beneficial entropy term, which predominantly caused pre‐organization in its binding conformation. We have shown, that among elements responsible for pre‐organization, stabilization between H−C5 l ‐fucose and ring oxygen O5 neighboring d ‐galactose moiety essential yields 7.4 kJ mol −1 . This effect could be further strengthened replacing 6,6,6‐trifluoro‐ leading an improved H‐bond 14.9 i.e., bioactive For series glycomimetics ), outcome confirmed high field NMR‐shifts Fuc X‐ray diffraction analysis co‐crystallized with as well isothermal titration calorimetry. Furthermore, electron‐withdrawing character CF 3 ‐group beneficially influences pharmacokinetic properties mimetics. Thus, acid‐stability, prerequisite gastrointestinal stability, substantially improved.

Language: Английский

Citations

3
Nanoarchitectonics of cello-oligosaccharides: A route toward artificial nanocelluloses DOI Creative Commons
Yuuki Hata, Takeshi Serizawa

Advances in Colloid and Interface Science, Journal Year: 2024, Volume and Issue: 336, P. 103361 - 103361

Published: Nov. 29, 2024

Language: Английский

Citations

3
A glycan foldamer that uses carbohydrate–aromatic interactions to perform catalysis DOI Creative Commons
Kaimeng Liu, Martina Delbianco

Nature Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Language: Английский

Citations

0
Controlling Glycan Folding with Ionic Functional Groups DOI Creative Commons

Nishu Yadav,

Ana Poveda,

Yadiel Vázquez Mena

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Glycans are intrinsically flexible molecules that can adopt many conformations. These often carry ionic functional groups influence glycan's conformational preferences, dynamics, and aggregation tendencies. Inspired by these mechanisms, we have engineered a glycan sequence whose secondary structure be precisely manipulated using groups. We strategically incorporated substituents into adopting hairpin conformation. Complementary stabilized the closed conformers, while repulsions shifted populations toward open forms. External stimuli, such as pH variations or enzyme addition, enabled us to dynamically control hairpin's opening closing. Additionally, changes in protonation states led aggregation, suggesting opportunities for creation of responsive glycan-based materials.

Language: Английский

Citations

0
The synergy of experimental and computational approaches for visualizing glycoprotein dynamics: Exploring order within the apparent disorder of glycan conformational ensembles DOI Creative Commons
Koichi Kato, Saeko Yanaka, Takumi Yamaguchi

et al.

Current Opinion in Structural Biology, Journal Year: 2025, Volume and Issue: 92, P. 103049 - 103049

Published: April 29, 2025

Understanding the dynamic behavior of glycoproteins is crucial for deciphering their biological roles. This review explores synergistic use experimental and computational methods to address this complex challenge. Glycans, with inherent flexibility structural diversity, pose significant obstacles traditional analysis. Innovative techniques offer valuable snapshots glycan conformations, but often lack context a physiological environment. Computational simulations provide atomic-level detail explore full range motions, require extensive resources validation. Integrating these approaches, by using data refine validate models, essential accurately capturing interplay between glycans proteins. combined strategy promises unlock deeper understanding glycoprotein function inform design novel therapeutics.

Language: Английский

Citations

0
Strengthening an Intramolecular Non‐Classical Hydrogen Bond to Get in Shape for Binding DOI Creative Commons
Norbert Varga, Martin Smieško, Xiaohua Jiang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: July 27, 2024

Abstract In this research article, we report on the strengthening of a non‐classical hydrogen bond (C−H⋅⋅⋅O) by introducing electron withdrawing groups at carbon atom. The approach is demonstrated example derivatives physiological E‐selectin ligand sialyl Lewis x ( 1 , sLe ). Its affinity mainly due to beneficial entropy term, which predominantly caused pre‐organization in its binding conformation. We have shown, that among elements responsible for pre‐organization, stabilization between H−C5 l ‐fucose and ring oxygen O5 neighboring d ‐galactose moiety essential yields 7.4 kJ mol −1 . This effect could be further strengthened replacing 6,6,6‐trifluoro‐ leading an improved H‐bond 14.9 i.e., bioactive For series glycomimetics ), outcome confirmed high field NMR‐shifts Fuc X‐ray diffraction analysis co‐crystallized with as well isothermal titration calorimetry. Furthermore, electron‐withdrawing character CF 3 ‐group beneficially influences pharmacokinetic properties mimetics. Thus, acid‐stability, prerequisite gastrointestinal stability, substantially improved.

Language: Английский

Citations

1