X-Pro peptides: Solution and solid-state conformation of benzyloxycarbonyl-(Aib-Pro)2methyl ester, a type I β-turn

✍ Scribed by Y. V. Venkatachalapathi; C. M. K. Nair; M. Vijayan; P. Balaram

• Publisher: Wiley (John Wiley & Sons)
• Year: 1981
• Tongue: English
• Weight: 671 KB
• Volume: 20
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.1981.360200604

✦ Synopsis

The synthesis of the tetrapeptide benzyloxycarbonyl(a-aminoisobutyryl-L-prolyl)zmethyl ester (Z-(Aib-Pro)z-OMe) and an analysis of its conformation in solution and the solid state are reported. Stepwise synthesis using dicyclohexylcarbodiimide leads to racemization a t Pro(2). Evidence for the presence of diastereomeric tetrapeptides is obtained from 270-MHz'H-nmr and 67.89-MHz T C -n m r . The all-L tetrapeptide is obtained by fractional crystallization from ethyl acetate. The NH of Aib( ) is shown to be involved in an intramolecular hydrogen bond by variable-temperature 'H-nmr and the solvent dependence of NH chemical shifts. The results are consistent with a @urn conformation with Aib(1) and Pro(2) at the corners stabilized by a 4 -+ 1 hydrogen bond. The molecule crystallizes in the space group P212121, with a = 8.839, b = 14.938, and c = 22.015 A. The structure has been refined to an R value of 0.051. The peptide backbone is all-trans, and a 4 -1 hydrogen bond, between the CO group of the urethane moiety and Aib(3) NH, is ohserved. Aib(1) and Pro(2) occupy the corner positions of a type 18-turn with @ = -55.4', $ = -31.3' for Aib(1) and @ = -71.6', J. = -38" for Pro(2). The tertiary amide unit linking Pro(2) and Aib(3) is significantly distorted from planarity (Am = 14.3').