The Distinct Conformational Landscapes of 4S-Substituted Prolines That Promote an endo Ring Pucker.

ABSTRACT: 4-Substitution on proline directly impacts protein main chain conformational preferences. The structural effects of N-acyl substitution and of 4-substitution were examined by NMR spectroscopy and X-ray crystallography on minimal molecules with a proline 4S-nitrobenzoate. The effects of N-acyl substitution on conformation were attenuated in the 4S-nitrobenzoate context, due to the minimal role of the n??* interaction in stabilizing extended conformations. By X-ray crystallography, an extended conformation was observed for most molecules. The formyl derivative adopted a ? conformation that is observed at the i+2 position of ?-turns. Computational analysis indicated that the structures observed crystallographically represent the inherent conformational preferences of 4S-substituted prolines with electron-withdrawing 4-position substituents. The divergent conformational preferences of 4R- and 4S-substituted prolines suggest their wider structure-specific application in molecular design. In particular, the proline endo ring pucker favored by 4S-substituted prolines uniquely promotes the ? conformation [(?, ?) ?(-80°, 0°)] found in ?-turns. In contrast to other acyl capping groups, the pivaloyl group strongly promoted trans amide bond and polyproline II helix conformation, with a close n??* interaction in the crystalline state, despite the endo ring pucker, suggesting its special capabilities in promoting compact conformations in ? due to its strongly electron-donating character.

SUBMITTER: Costantini NV 

PROVIDER: S-EPMC6710147 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature