α,β-Dehydroamino acid residues contain a double bond between the Cα
atoms. Due to this structural feature they have the capacity to induce ordered structures in peptides. These structures depend on the type, content and mutual location of Δ-amino acid residues in the peptide sequence. The conformation-stabilizing effect is very pronounced in the case of the ΔPhe residue. The presence of one or more ΔPhe residues results in the β-turn conformation in short peptides (Główka et al.
; Główka, 1988
; Aubry et al.
) and the 310
helical arrangement in longer peptides (Rajashankar et al.
; Padmanabhan & Singh, 1993
; Rajashankar, Ramakumar, Jain & Chauhan, 1995
; Rajashankar, Ramakumar, Mal et al.
; Jain et al.
). The preferred values for the torsion angles ϕ and ψ fall predominantly into the regions of 80 and 0, 60 and 140, and 60 and 30°, respectively, and their enantiomeric values (Singh & Kaur, 1996
This paper follows previous research on the conformational preferences of ΔPhe residues (Makowski et al.
, and references therein). We present the structures of two pentadehydropeptides with two ΔPhe residues, viz.
, and Boc0
. The peptides differ only in the configuration of the ΔPhe residues. Both peptides crystallize in the same space group, P
, with one molecule in the asymmetric unit. Additionally, peptide (I)
cocrystallizes with one molecule of methanol in the asymmetric unit. A comparison of the crystal structures of both peptides will allow evaluation of the impact of individual ΔPhe isomers on the conformational preferences of the peptides. The atom labelling is the same in both structures.
All amino acids, in both structures, are linked trans
to each other. The deviations from ideal ω = 180° do not exceed 10°. Blocking groups adopt transoidal
conformations, as indicated by the values of the ω0
(N1—C5—O1—C1) and ϕ0
(C6—N1—C5—O1) torsion angles (Tables 1 and 3). The Cα
distances (C8=C9 and C19=C20) are classical double-bond lengths (Tables 1 and 3) and correspond well with the results of other X-ray crystallographic studies of dehydropeptides (Główka et al.
; Ejsmont et al.
; Makowski et al.
Table 1 Selected geometric parameters (Å, °) for (I)
Table 3 Selected geometric parameters (Å, °) for (II)
Because of the unsaturated character of the Cα
bond, the side chains of the ΔPhe residues are much closer to the main-chain atoms compared with their saturated counterparts. This feature results in some geometric distortions characteristic of dehydropeptide structures (Główka et al.
). Systematic shortening of the N—Cα
(N2—C8 and N4—C19), Cα
(C8—C16 and C19—C27) and Cβ
(C9—C10 and C20—C21) single bonds (Tables 1 and 3) is observed, which may be caused by extended delocalization of the π electron system. The values of the N2—C8—C16 [118.8 (2) and 114.67 (18)° for (I)
, respectively] and N4—C19—C27 [117.1 (2) and 114.04 (18)° for (I)
, respectively] bond angles are smaller than the regular trigonal value of 120°, which is clearly understandable owing to the steric interactions between the main chain and the side chains of ΔPhe. It is interesting that these effects influence analogous angles in both peptides to the same extent, regardless of the location of the aromatic rings.
Another characteristic consequence of the short distance between the aromatic rings and the peptide chain is a considerable opening of the valence angles Cα
to relax the steric strain (Główka, 1988
). This trend explains the increased values of the Cα
bond angles for both structures. These angles are the same in both ΔPhe residues in each structure and agree to within one standard deviation between (I)
. In the case of (I)
, these angles for ΔZ
are C8—C9—C10 = 131.4 (3)° and C19—C20—C21 = 131.4 (3)°, respectively, and for ΔE
they are C8—C9—C10 = 129.9 (2)° and C19—C20—C21 = 129.9 (2)°, respectively. The torsion angles χ2
= −176.9 (2)° and χ4
= −176.0 (2)° between N—Cα
and the aromatic system, and χ2,1
= −155.1 (3)°, χ2,2
= 25.4 (4)°, χ4,1
= 20.7 (4)° and χ4,2
= −159.7 (2)°, indicate that in the case of (II)
the side chains of both ΔPhe residues are almost planar, while for (I)
the torsion angles χ4
= 0.2 (5)°, χ4,1
= −19.8 (5)° and χ4,2
= 162.9 (3)° show that only the side chain of ΔPhe4
is planar. The ΔPhe2
residue side chain adopts a trans
conformation, with torsion angles χ2,1
= −152.6 (3)° and χ2,2
= 30.8 (5)°.
The presence of two ΔZ
Phe residues in (I)
induces the occurrence of two overlapping β-turns. The first is formed by the ΔZ
residues, with torsion angles ϕ2
= 50.4 (4)° and ψ2
= 20.0 (4)°, and ϕ3
= 54.7 (4)° and ψ3
= 26.7 (4)°, respectively. The second turn includes the Gly3
residues, with torsion angles ϕ3
= 50.4 (4)° and ψ3
= 20.0 (4)°, and ϕ4
= 68.7 (3)° and ψ4
= 17.4 (4)°, respectively. The torsion angles indicate that these β-turns are of type III′ (Lewis et al.
). They are stabilized by 4→1 hydrogen bonds between the NH group of ΔZ
and the CO group of Gly1
, and between the NH group of Gly5
and the CO group of ΔZ
(Table 2). The two β-turns of type III′ in (I)
are the same as in the previously reported crystal structure of the Boc0
–OMe pentapeptide, which differs from (I)
only in the methanolate group at the C terminus (Makowski et al.
). The molecular structure of peptide (I)
is presented in Fig. 1(a
) and its packing diagram is shown in Fig. 2.
Table 2 Hydrogen-bond geometry (Å, °) for (I)
Figure 1 The molecular structures of peptides (a) (I) and (b) (II), showing the atom-numbering schemes. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii. Hydrogen bonds are shown (more ...)
Figure 2 A packing diagram for peptide (I). Hydrogen bonds are represented by dashed lines. Symmetry codes are as given in Table 2.
The situation is somewhat different in the case of (II)
. There is only one β-turn at the ΔE
residues, stabilized by a 4→1 hydrogen bond between the NH group of ΔE
and the CO group of Gly1
(Table 4). This β-turn is additionally stabilized by a C—H
π interaction. The ϕ and ψ angles of these residues are 33.2 (3) and −119.6 (2)°, and −83.2 (3) and −5.3 (3)°, respectively. These values correspond well with a type-II β-turn (Lewis et al.
). Deviations from the ideal torsion angles for this β-turn (−60 and 120°, and 80 and 0°) are not larger than 26°, compared with a maximum acceptable deviation of 40° (Lewis et al.
). In addition, the C-terminal amino acid residues adopt a conformation similar to a type-IV β-turn. The whole structure is stabilized by inter- and intramolecular hydrogen bonds of various types, namely O—H
O and C—H
π (Table 4). However, the conformational constraints are not sufficient for a second β-turn to be formed. The molecular structure of peptide (II)
is presented in Fig. 1(b
Table 4 Hydrogen-bond geometry (Å, °) for (II)
A comparison of (I)
reveals that a ΔZ
Phe residue is a more effective inducer of folded structures than a ΔE
Phe residue. The insertion of two ΔZ
Phe residues in (I)
gives rise to the formation of two β-turns and the structure is stabilized by two intramolecular 4→1 hydrogen bonds. In the case of (II)
, there is only one β-turn stabilized by a hydrogen bond and the resulting conformation is more distorted, and this is reflected in the greater deviations from ideal dihedral angles for the β-turns. The previously reported crystal structure of a closely related peptide, viz.
Phe–Gly–OMe (Makowski et al.
), shows that in the case of a ΔE
residue the formation of a second β-turn is hindered and deviations from ideal values for the torsion angles ϕ and ψ are increased. A type-II β-turn for the ΔZ
residues, and a type-IV β-turn for Gly3
, was observed. The ΔE
residue in (II)
does not induce a β-turn, as in the case of Boc0
–OMe. A β-turn at the ΔE
residue has been observed for Boc0
-NA·EtOH (Makowski et al.
), due to the presence of the additional H-atom donor, p
-NA), which forms a hydrogen bond with the CO group of Gly3
The atypical location of the H atom of the C-terminal carboxyl group, H8, merits further discussion. In (II)
it is directed to the opposite side compared with the analogous atom in (I)
. The O8 atoms in both molecules take part in hydrogen bonds. In the case of (II)
, atom H8 participates in the intermolecular N2—H2
O8(1 − x
) hydrogen bond (Table 4). The formation of this bond requires a relocation of the H atom. What is more, amide atom H2 of another molecule of (II)
in that hydrogen bond corresponds to the position of the carboxyl H atom in (I)
. Therefore, we suspect some competition between the O8—H8 covalent bond and the N2—H2
O8(1 − x
) hydrogen bond which results in moving atom H8 to the alternative position.
Further information can be derived from a detailed analysis of the packing diagrams of both molecules. The crystal structure stabilizing effect compensates for the energy loss resulting from the unusual position of the H atom in (II)
. Additionally, the position of atom H8 in (II)
is stabilized by the O8—H8
) hydrogen bond. This unusual position of the hydroxy H atom is rarely encountered. As reported recently, it occurs when additional stabilization is provided by other interactions (Videnova-Adrabinska et al.
). In the discussed case, the H atom switches its orientation to approach the lone pair of another hydroxy O atom.