title: Can N-methylated amino acids serve as substitutes for prolines in conformational design of cyclic pentapeptides?
abstract: The incorporation of proline into cyclic peptides seems to be the most promising way to induce beta-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.
authors.affiliation: Center for Integrated Protein Science at the Department Chemie, Technische Universität München, Lichtenbergstrasse 4, Garching, D-85747 Germany.
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Laufer
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chatterjee
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Frank
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D000596:Amino Acids; D010456:Peptides, Cyclic; D011392:Proline