The tripeptide N-Cbz-βGly-Gly-Gly-Obz

The title peptide, N-benzyloxycarbonyl-β-glycylglycylglycine benzyl ester, C22H25N3O6, contains a non-proteinogenic amino acid residue, β-glycine, which is a homologated analogue of glycine. In the molecular structure, β-glycine adopts an extended conformation with a trans conformation about its Cβ—Cα bond. The second glycine residue adopts an extended conformation while the third glycine residue adopts a helical conformation. In the crystal, three N—H⋯O hydrogen bonds, two involving the same carbonyl O atom as acceptor, results in an infinite two-dimensional network parallel to the bc plane.


S1. Chemical context
Insertion of methylene units to the backbone of α-amino acids generates a family of amino acids referred to as ω-amino acids (Cheng et al., 2001;Seebach et al., 2004). β-Amino acids are obtained when a single methylene unit is added to the backbone of an α-amino acid. Compounds containing β-amino acids are ubiquitously found in biological systems (Seebach et al., 2004). The simplest β-amino acid, β-glycine, is a component of co-enzyme A, pantothenic acid and carnosine. β-amino acids have an additional degree of torsional freedom about the C β -C α bond (θ) and this increases the conformational possibilities of peptides formed of β-amino acids.
In case of β-amino acids, information regarding the conformational preferences can only be obtained by crystallographic characterization of synthetic peptides unlike in case of α-amino acids where such information can be gathered from the crystal structures of proteins. This paper presents the crystallographic characterization of a synthetic peptide containing a β-glycine residue.

S2. Molecular Conformation
The first two glycine residues of the peptide molecule adopt extended conformations while the third glycine residue adopts a helical conformation. βGly(1) adopts torsion angle values φ 1 = 146.5° and ψ 1 = -155.9°. Trans conformation is observed about the C β -C α bond of the βGly(1) residue. Gly(2) adopts torsion angles φ 2 = -61.0° and ψ 2 = 151.4° while Gly(3) adopts torsion angle values φ 3 = -137.2° and ψ 3 = -170.4°. Since the crystal structure is that of an achiral peptide crystallized in a centrosymmetric space group, the choice of sign for torsion angles is arbitrary. There are no intramolecular hydrogen bonds in the crystal structure.

S3. Supramolecular features
An analysis of the packing of molecules in the crystal revealed the presence of three intermolecular hydrogen bonds.
Molecules related by the symmetry (-x, 1/2 + y, 1/2 -z) associate through hydrogen bonds resulting in columns of hydrogen bonded molecules extending along the crystallographic b-direction. Aggregation also occurs via intermolecular bifurcated hydrogen bonding involving a carbonyl oxygen and two donor NH groups.

S4. Synthesis and crystallization
The title compound was purchased commercially. Plate-like crystals of the title compound were obtained by slow evaporation from methanol/water solution.

S5. Refinement
The N-bound H atoms and H-atoms bound to C2A could be located from difference Fourier maps. The remaining Cbound H atoms were fixed geometrically in calculated positions and refined as riding atoms. During refinement, H-atoms attached to aromatic rings were positioned with C-H = 0.93 Å and U iso (H) = 1.2U eq (C) while methylene H-atoms were positioned with C-H = 0.97 Å and U iso (H) = 1.2U eq (C).

Figure 1
Thermal Ellipsoid plot of NCbz-β Gly-Gly-Gly-Obz drawn at 50% probability level. Hydrogen atoms have been omitted for clarity. Atomic labeling and definition of backbone torsion angles in case of β-residues.

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.