11th Naples Workshop on Bioactive Peptides
Can N-methylated amino acids serve as substitutes for prolines in conformational design of cyclic pentapeptides?†
Article first published online: 4 NOV 2008
Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Special Issue: 11th Naples Workshop on Bioactive Peptides
Volume 15, Issue 3, pages 141–146, March 2009
How to Cite
Laufer, B., Chatterjee, J., Frank, A. O. and Kessler, H. (2009), Can N-methylated amino acids serve as substitutes for prolines in conformational design of cyclic pentapeptides?. J. Peptide Sci., 15: 141–146. doi: 10.1002/psc.1076
- Issue published online: 2 FEB 2009
- Article first published online: 4 NOV 2008
- Manuscript Accepted: 22 AUG 2008
- Manuscript Revised: 19 AUG 2008
- Manuscript Received: 17 JUL 2008
- International Graduate School of Science and Engineering (IGSSE) of the Technische Universität München
- N-methylated peptides;
- N-methylated amino acids;
- proline-containing peptides;
- cyclic peptides;
- peptide conformation;
- tertiary amide bond
The incorporation of proline into cyclic peptides seems to be the most promising way to induce β-turn structures. Recently, however, it was shown that N-methylated amino acids might be even better suited than proline for introducing turn structures. Another property of proline, the ability to effect cis-peptide bonds, has also been reported for N-methylated amino acids. These findings raise the question if it might be possible to replace a proline by an N-methylated amino acid without altering the desired conformational features. The most important benefit of replacing proline by an N-methylated residue is that one recovers the side-chain functionalities, which could be used for enhancing binding selectivity, or to tune a cyclic peptide concerning its pharmacological properties.
Here, we compare cyclic peptides containing one or two prolines or N-methylated alanines and a combination of both with respect to preferred conformations and cis-peptide bonds. In addition, the positions have been investigated where an N-alkylated amino acid has to be incorporated to mimic structural aspects usually introduced by proline residues. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.