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Can N ‐methylated amino acids serve as substitutes for prolines in conformational design of cyclic pentapeptides?
Author(s) -
Laufer Burkhardt,
Chatterjee Jayanta,
Frank Andreas O.,
Kessler Horst
Publication year - 2009
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1076
Subject(s) - proline , amino acid , cyclic peptide , chemistry , peptide , residue (chemistry) , stereochemistry , peptide bond , side chain , alkylation , amino acid residue , turn (biochemistry) , biochemistry , combinatorial chemistry , peptide sequence , organic chemistry , gene , catalysis , polymer
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.