Enantioselective molecular recognition between β-sheets

This communication asks whether homochiral or heterochiral interaction is preferred between enantiomeric β-sheets and finds that homochiral pairing is strongly preferred. Interactions between β-sheets occur widely among proteins through pairing of the hydrogen-bonding edges. Although the hydrogen-bonding edges of both L- and D-β-sheets put forth the same pattern of hydrogen-bond donor and acceptor groups, the side chains point in opposite directions. Homochiral pairing of β-sheets generates structures in which the pleats and side chains of adjacent β-strands are parallel to each other, while heterochiral pairing of β-sheets generates structures in which the pleats and side chains are antiparallel. To test which pairing is preferred, we have prepared and studied the interactions of β-sheets 1a?d, which comprise all l-amino acids, and β-sheets 2a?c, which comprise all d-amino acids. Previous studies in our laboratory have established that these compounds form well-defined dimers in organic solvents. In the current study, 1H NMR experiments establish that when the L-β-sheets (1) are mixed with the enantiomeric D-β-sheets (2), homochiral β-sheet dimers predominate, and only small quantities of heterochiral β-sheet dimers form. Ratios of homochiral and heterochiral dimers ranging from 95.8:4.2 to 98.5:1.5 are measured in CDCl3 at 253 K, which correspond to statistically corrected free-energy differences of 3.1?4.2 kcal/mol (0.6?0.8 kcal/mol per interacting residue). Possible explanations for the high enantioselectivity of molecular recognition between β-sheets include favorable nonbonded contacts between the adjacent β-strands of the homochiral β-sheets and poor fit of the heterochiral β-strands, which should twist in opposite directions. Copyright © 2004 American Chemical Society.