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Peptide‐Based Carbohydrate Receptors
Author(s) -
Rauschenberg Melanie,
Bandaru Sateesh,
Waller Mark P.,
Ravoo Bart Jan
Publication year - 2014
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.201303777
Subject(s) - isothermal titration calorimetry , chemistry , non covalent interactions , monosaccharide , hydrogen bond , antiparallel (mathematics) , aqueous solution , circular dichroism , hydrophobic effect , nuclear magnetic resonance spectroscopy , intermolecular force , peptide , stereochemistry , crystallography , molecule , organic chemistry , biochemistry , physics , quantum mechanics , magnetic field
Abstract A broad spectrum of physiological processes is mediated by highly specific noncovalent interactions of carbohydrates and proteins. In a recent communication we identified several cyclic hexapeptides in a dynamic combinatorial library that interact selectively with carbohydrates with high binding constants in water. Herein, we report a detailed investigation of the noncovalent interaction of two cyclic hexapeptides (Cys‐His‐Cys (which we call HisHis) and Cys‐Tyr‐Cys (which we call TyrTyr)) with a selection of monosaccharides and disaccharides in aqueous solution. The parallel and antiparallel isomers of HisHis or TyrTyr were synthesized separately, and their interaction with monosaccharides and disaccharides in aqueous solution was studied by isothermal titration calorimetry, NMR spectroscopic titrations, and circular dichroism spectroscopy. From these measurements, we identified particularly stable complexes ( K a >1000 M −1 ) of the parallel isomer of HisHis with N ‐acetylneuraminic acid and with methyl‐α‐ D ‐galactopyranoside as well as of both isomers of TyrTyr with trehalose. To gain further insight into the structure of the peptide–carbohydrate complexes, structure prediction was performed using quantum chemical methods. The calculations confirm the selectivity observed in the experiments and indicate the formation of multiple intermolecular hydrogen bonds in the most stable complexes.