Rotational Barriers ofcis/transIsomerization of Proline Analogues and Their Catalysis by Cyclophilin

• DOI: 10.1021/ja970606w
• Publication Date: 2002-07-26T05:09:17Z
• Authors: Dorothee Kern; Mike Schutkowski; Torbjörn Drakenberg
• Keywords: Polyproline helix

The rotational barriers for cis/trans isomerization of different proline analogues have been investigated by dynamic 1H NMR spectroscopy. To this end the (S)-azetidine-2-carboxylic acid (Aze), (S)-piperidine-2-carboxylic (Pip), (R)-thiazolidine-4-carboxylic (4-Thz), (4R)-2-methylthiazolidine-4-carboxylic (2Me4-Thz), (R)-thiazolidine-2-carboxylic (2-Thz), (S)-oxazolidine-4-carboxylic (4-Oxa), (4S,5R)-5-methyloxazolidine-4-carboxylic (5Me4-Oxa), and (2S,4R)-4-hydroxypyrrolidine-2-carboxylic (Hyp) several N-alkylated amino acids were incorporated into sequences Ala-Yaa-(4-)nitroanilide Ala-Gly-Yaa-Phe-(4-)nitroanilide. line-shape analyses various cis trans proton signals these peptides performed at temperatures, rate constants fitted to Eyring equation. all cyclic except hydroxyproline found be lower than that about 10 kJ/mol, whereas noncyclic showed similar observed proline. In addition, ability cytosolic porcine kidney cyclophilin (Cyp18), a member peptidyl prolyl isomerase family, catalyze peptide bond preceding was investigated. By we proved efficient catalysis Cyp18 Aze, 4-Thz, 2-Thz.