title: X-ray structure analysis reveals β-turn mimicry by N-amino-imidazolidin-2-ones.
abstract: The conformation of the N-amino-imidazolidin-2-one (Aid) peptidomimetic was investigated using NMR spectroscopy and X-ray crystallography. In solution, the tetrapeptide model p-bromobenzoyl-Aid-l-Phe-N'-iso-propylamide (1) exhibited shielded and solvent exposed amide protons indicative of a turn conformation. In the crystal lattice of 1, four turn conformers were present in the unit cell differing primarily by the ring puckering of the Aid residue. Two pairs of β-turn conformers were observed each possessing an intramolecular ten-member hydrogen bond between the benzamide carbonyl and iso-propylamine NH moieties. The pairs had types II and II' β-turn geometry that differed slightly about the ϕ and ψ torsion angles. Moreover, the X-ray analysis of 1 has been compared with that of the related unsaturated N-amino-imidazolin-2-one (Nai) analogs indicating the influences of ring flattening and substituents on conformation. Insertion of the preorganized Aid structure into biologically active peptides has thus been shown to offer a potentially valuable means for exploring the importance of turn geometry for activity, particularly in drug discovery.
authors: Département de Chimie, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, QC, Canada, H3C 3J7.|Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139.
authors: Ngoc-Duc
authors: ND
authors: Doan
authors: Département de Chimie, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, QC, Canada, H3C 3J7.
authors: William D
authors: WD
authors: Lubell
mesh_terms: D018360:Crystallography, X-Ray; D048289:Imidazolidines / Q000737:chemistry*; D018716:Molecular Mimicry
chemical_list: D048289:Imidazolidines; C004916:ethylene urea
keywords: N-amino-imidazolidin-2-one; peptidomimetic; β-turn mimetic