X-ray structure analysis reveals β-turn mimicry by N-amino-imidazolidin-2-ones

Biopolymers
Ngoc-Duc Doan, William D Lubell

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.

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Citations

Jun 10, 2017·Accounts of Chemical Research·Ramesh ChingleWilliam D Lubell
May 15, 2020·Organic Letters·Selma Crecente-GarciaAndrew R Thomson

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