Gueret, Stephanie and Wagner, Beatrix (2015) A Cyclic Carbo-Isosteric Penta-Depsipeptide: cyclo(Phe1–D-Ala2–Gly3–Phe4–APO5). Acta Crystallographica Section E, E71. pp. 113-116.

Abstract

The title compound, cyclo(Phe1–D-Ala2–Gly3–Phe4–APO5), C26H32N4O5, is a cyclic penta-peptidomimetic analogue containing a novel 2-amino propyl lactone (APO) motif, which displays the same number of atoms as the native amino acid glycine and has a methyl group in place of the carbonyl oxygen. The crystal structure presented here allows the analysis of the secondary structure of this unprecedented cyclic carbo-isosteric depsipeptide. The conformation of the central ring is stabilized by an intramolecular N–H···O hydrogen bond between the carbonyl O atom of the first residue (Phe1) and the amide group H atom of the fourth residue (Phe4). Based on the previously reported hydrogen bond and on the values of the torsion angles φ and ψ, the loop formed by the first, second, third and fourth residues (Phe1, D-Ala2, Gly3 and Phe4) can be classified as a type II' β-turn. The loop around the new peptidomimetic motif, on the other hand, resembles an open γ-turn containing a loose N–H···O hydrogen bond between the carbonyl group O atom of the fourth residue (Phe4) and the amide unit H atom of the first residue (Phe1) (d = 3.34 Å). In the crystal, the peptidomimetic molecules are arranged in chains along the crystallographic b axis. Within such a chain, the molecules of the structure are linked via N–H···O hydrogen bonds between the amide group H atom of the secondary residue (D-Ala2) and the carboxy unit O atom of the fourth residue (Phe4) in the neighboring molecule. The newly formed methyl stereocentre (C10) of the novel APO peptidomimetic motif (APO5), obtained using a ring closing reductive amination reaction, adopts an R configuration.

Item Type:	Article
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/23891