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Scope of amino acid recognition by cucurbit[8]uril

Journal of Inclusion Phenomena and Macrocyclic Chemistry volume 62, pages 251–254 (2008)Cite this article

Abstract

This paper describes the molecular recognition of amino acids by cucurbit[8]uril (Q8) and by the 1:1 complex between Q8 and methyl viologen (MV) in purely aqueous solution. These hosts are known to bind aromatic peptides with high affinity and sequence specificity, but prior work has focused on only a small subset of amino acids. In an effort to elucidate the scope and limitations of amino acid recognition by Q8 and Q8•MV, a comprehensive examination of the 20 genetically encoded amino acids was carried out by 1H NMR spectroscopy and isothermal titration calorimetry. We find that both Q8 and Q8•MV bind measurably to only tryptophan, phenylalanine, and tyrosine. These results demonstrate that Q8 and Q8•MV are highly selective in the context of all genetically encoded amino acids and are therefore promising for the development of recognition-intensive applications involving peptides, proteins, and proteomes.

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Notes

  1. We used the L-enantiomer of arginine, cysteine, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan, tyrosine, and valine; and the DL-racemate of alanine, asparagine, aspartic acid, glutamine, glutamic acid. The 50% reduction in concentration for the L-enantiomer in these five racemic mixtures was not considered to be significant given that no binding was observed in all cases.

  2. Cong et al. report a 1:1 (Q8:amino acid) stoichiometry for Q8 with tryptophan and tyrosine and a 2:1 stoichiometry with phenylalanine on the basis of continuous variation experiments by UV-visible spectroscopy. This method, however, does not provide reliable stoichiometric constants if higher order dissociation constants are significantly greater than the working concentration.

  3. The methodology used for determining the thermodynamic constants for the formation of ternary complexes with Q8 is described in detail in reference 11.

  4. We have an unpublished crystal structure of Q8 bound to two copies of Trp-Gly-Gly, which shows that both indoles cannot fit completely within the cavity of Q8 while maintaining contacts between N-terminal ammonium groups and proximal carbonyl groups on Q8.

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Acknowledgements

This research was funded in part by grants from the Welch Foundation (W-1640) and Research Corporation (CC6517). We also thank the Welch Foundation for a departmental grant that supported summer research for PR. We thank Dr. Joseph J. Reczek and Prof. Jerry Yang for helpful discussions and Lisa M. Ryno and Gretchen A. Vincil for technical support.

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  1. Department of Chemistry, Trinity University, San Antonio, TX, 78212, USA

    P. Rajgariah & A. R. Urbach

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  1. P. Rajgariah
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  2. A. R. Urbach
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Correspondence to A. R. Urbach.

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Rajgariah, P., Urbach, A.R. Scope of amino acid recognition by cucurbit[8]uril. J Incl Phenom Macrocycl Chem 62, 251–254 (2008). https://doi.org/10.1007/s10847-008-9464-y

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Keywords

  • Cucurbit[n]uril
  • Cucurbit[8]uril
  • Molecular recognition
  • Amino acid
  • Amino acid recognition
  • Aqueous solution
  • Tryptophan
  • Phenylalanine

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