Document Type
Post-Print
Publication Date
10-19-2005
Abstract
The molecular recognition of peptides and proteins in aqueous solution by designed molecules remains an elusive goal with broad implications for basic biochemical research and for sensors and separations technologies. This paper describes the recognition of N-terminal tryptophan in aqueous solution by the synthetic host cucurbit[8]uril (Q8). Q8 is known to form 1:1:1 heteroternary complexes with methyl viologen (MV) and a second aromatic guest. Here, the complexes of Q8·MV with (i) the four natural aromatic α-amino acids, (ii) four singly charged tryptophan derivatives, and (iii) four tryptophan-containing tripeptides were characterized by isothermal titration calorimetry, mass spectrometry, and UV−visible, fluorescence, and 1H NMR spectroscopy. We find that Q8·MV binds Trp−Gly−Gly with high affinity (Ka = 1.3 × 105 M-1), with 6-fold specificity over Gly−Trp−Gly, and with 40-fold specificity over Gly−Gly−Trp. Analysis of the nine indole-containing compounds suggests that peptide recognition is mediated by the electrostatic charge(s) proximal to the indole, and that the mode of binding is consistent for these compounds. Complex formation is accompanied by the growth of a visible charge-transfer band and the quenching of indole fluorescence. These optical properties, combined with the stability and selectivity of this system, are promising for applications in sensing and separating specific peptides.
DOI
10.1021/ja0548440
Publisher
American Chemical Society
Repository Citation
Bush, M. E., Bouley, N. D., & Urbach, A. R. (2005). Charge-mediated recognition of N-terminal tryptophan in aqueous solution by a synthetic host. Journal of the American Chemical Society, 127(41), 14511-14517. https://doi.org/10.1021/ja0548440
Publication Information
Journal of the American Chemical Society