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cis‐trans Peptide‐Bond Isomerization in α ‐Methylproline Derivatives
Author(s) -
Torbeev Vladimir Y.,
Fumi Erik,
Ebert MarcOlivier,
Schweizer W. Bernd,
Hilvert Donald
Publication year - 2012
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201200483
Subject(s) - chemistry , proline , isomerization , conformational isomerism , peptide bond , peptide , stereochemistry , cis–trans isomerism , polyproline helix , molecule , amino acid , catalysis , organic chemistry , biochemistry
Abstract α ‐Methyl‐ L ‐proline is an α ‐substituted analog of proline that has been previously employed to constrain prolyl peptide bonds in a trans conformation. Here, we revisit the cis ‐ trans prolyl peptide bond equilibrium in derivatives of α ‐methyl‐ L ‐proline, such as N ‐Boc‐protected α ‐methyl‐ L ‐proline and the hexapeptide H‐Ala‐Tyr‐ α MePro‐Tyr‐Asp‐Val‐OH. In Boc‐ α ‐methyl‐ L ‐proline, we found that both cis and trans conformers were populated, whereas, in the short peptide, only the trans conformer was detected. The energy barrier for the cis ‐ trans isomerization in Boc‐ α ‐methyl‐ L ‐proline was determined by line‐shape analysis of NMR spectra obtained at different temperatures and found to be 1.24 kcal/mol (at 298 K) higher than the corresponding value for Boc‐ L ‐proline. These findings further illuminate the conformationally constraining properties of α ‐methyl‐ L ‐proline.