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Binding Studies on a Library of Induced‐Fit Synthetic Carbohydrate Receptors with Mannoside Selectivity
Author(s) -
Palanichamy Kalanidhi,
Bravo M. Fernando,
Shlain Milan A.,
Schiro Frank,
Naeem Yasir,
Marianski Mateusz,
Braunschweig Adam B.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201803317
Subject(s) - glycan , chemistry , receptor , affinities , stereochemistry , binding affinities , binding selectivity , selectivity , carbohydrate conformation , molecular recognition , combinatorial chemistry , biochemistry , nuclear magnetic resonance spectroscopy , glycoprotein , molecule , organic chemistry , catalysis
Synthetic carbohydrate receptors could serve as agents for disease detection, drug delivery, or even therapeutics, however, they are rarely used for these applications because they bind weakly and with a preference towards the all‐equatorial glucosides that are not prevalent on the cell surface. Herein the binding of 8 receptors with 5 distinct octyloxy pyranosides, which was measured by mass spectrometry and by 1 H NMR titrations in CD 2 Cl 2 at 298 K, is reported, providing binding affinities that vary from ≈10 1 –10 4 m −1 . Although the receptors are promiscuous, 1 shows selectivity for β‐Man at a ratio of 103:1 β‐Man:β‐Gal, receptors 2 – 4 and 6 have preference for α‐Man, 5 is selective for β‐Gal, and 10 prefers α‐Glc (Man=mannose; Gal=galactose, Glc=glucose). A variety of 1D and 2D NMR, and computational techniques were used to determine the thermodynamic binding parameters (Δ H o and Δ S o ) and the structure of the host–guest complex, revealing that dimeric receptor 10 binds β‐Man with increased enthalpy, but a larger entropic penalty than 1 . The first‐principles modelling suggests that 10 ⋅β‐Man forms an inclusion‐type complex where the glycan engages both monomeric subunits of 10 through H‐bonding and C−H⋅⋅⋅π interactions. Like natural glycan‐binding proteins, these receptors bind pyranosides by accessing multivalent and cooperative interactions, and these studies suggest a new approach towards biomimetic synthetic carbohydrate receptors, where conformational flexibility and promiscuity are incorporated into design.