Kubik Group

Research - Cyclopeptides - Cation Recognition

Cyclic hexapeptides with 3-aminobenzoic acid subunits bind quaternary ammonium ions in chloroform. The cation affinity of a cyclopeptide containing glutamic acid residues is, however, small.1 One reason is the conformational flexibility of this compound that is caused by relatively free rotations around the bonds at the glutamic acid C(α) atoms. As a consequence of these rotations, several dish-shaped cyclopeptide conformations differing in the orientation of the aromatic subunits equilibrate in solution. The peptide is therefore poorly preorganized for cation binding.

conformations

Rotations around one bond at the C(α) atoms is prevented in a cyclopeptide containing proline instead of glutamic acid subunits. In spite of the overall reduced conformational flexibility of this compound rotations are possible at the secondary amide groups because intramolecular hydrogen bonds prevent this motions to occur. The proline containing peptide is still better preorganization for guest binding and forms more stable complexes with quaternary ammonium ions than the glutamic acid containing one.2

conformations

Rotation around the secondary amide groups is prevented in proline-derived cyclopeptides containing substituents in the 4-position of the aromatic subunits, which can form intramolecular hydrogen bonds to the neighboring NH groups. Such peptides thus adopt conformations in solution optimal for complex formation even in the absence of cationic substrates.3

conformations

The highest cation affinity was observed for a peptide with methoxycarbonyl substituents whose crystal structure is depicted below.3,4

crystal

[For an interactive version of the crystal structure click here]

The chirality of the cyclopeptides also allows for enantioselective recognition of chiral quaternary ammonium ions.5

References

  1. S. Kubik J. Am. Chem. Soc. 1999, 121, 5846-5855.
  2. S. Kubik, R. Goddard J. Org. Chem. 1999, 64, 9475-9486.
  3. S. Kubik, R. Goddard Eur. J. Org. Chem. 2001, 311-322.
  4. S. Kubik, R. Goddard Chem. Commun. 2000, 633-634.
  5. G. Heinrichs, L. Vial, J. Lacour, S. Kubik Chem. Commun. 2003, 1252-1253.

Last change: 19-05-05. Email

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