Helical templating of oligopeptides by cyclodextrin dimers

beta-cyclodextrin-based receptors were synthesized and tested for their ability to induce a helical fold in peptides bearing hydrophobic amino acid residues in the i, i + 11- or i, i + 14-positions. Circular dichroism experiments revealed that a dimeric beta-cylodextrin receptor synthesized from a [1,1'-biphenyl]-4,4'-dithiol core demonstrated an ability to fold a designed peptide bearing the artificial amino acid L-p-t-butylphenylalanine in the i, i + 11-positions, while other dimeric and monomeric receptors failed to do so. Titration studies were performed using both circular dichroism and calorimetry, the analysis of which yielded an apparent K,, on the order of 10(4)-10(5) M-1. However, no evidence could be obtained for helical folding with a peptide carrying tryptophan residues in place of the p-t-butylphenylala nine units. Our studies suggest that receptors of this type may be useful in molecular recognition of hydrophobic, already alpha-helical peptides in aqueous solution. (C) 2003 Elsevier Science Ltd. All rights reserved.